Pair Name	Ursolic acid, Doxorubicin
Partner Name	Ursolic acid
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Down-regulation	Phosphorylation	MTOR	hsa2475
	Down-regulation	Expression	PPARGC1A	hsa10891
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Up-regulation	Expression	ROS1	hsa6098
	Down-regulation	Expression	SLC2A1	hsa6513
In Vitro Model	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
Result	Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction

Pair Name	Ursolic acid, Doxorubicin
Partner Name	Ursolic acid
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CCN2	hsa1490
	Down-regulation	Expression	CCND1	hsa595
	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CDK4	hsa1019
	Down-regulation	Expression	CDK6	hsa1021
	Down-regulation	Phosphorylation	GSK3B	hsa2932
	Down-regulation	Expression	MMP9	hsa4318
	Up-regulation	Phosphorylation	MOB1A	hsa55233
	Up-regulation	Expression	MST1	hsa4485
	Up-regulation	Expression	MST2	hsa6788
	Down-regulation	Expression	MYC	hsa4609
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PLAU	hsa5328
	Up-regulation	Expression	SAV1	hsa60485
	Up-regulation	Phosphorylation	YAP1	hsa10413
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
In Vivo Model	HCT116 cells (1×10⁷) in 100 µl Matrigel were injected into the flank area of the mice.
Result	UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

Pair Name	Triptolide, Doxorubicin
Partner Name	Triptolide
Disease Info	[ICD-11: 2B33.4]	Leukemia		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Down-regulation	Expression	GPX4	hsa2879
	Down-regulation	Expression	NFE2L2	hsa4780
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens (Human)	CVCL_0002
Result	The present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolide‑induced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.

Pair Name	Thymoquinone, Doxorubicin
Partner Name	Thymoquinone
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	CDH13	hsa1012
	Down-regulation	Expression	MKI67	hsa4288
In Vitro Model	HuT 102	Mycosis fungoides	Homo sapiens (Human)	CVCL_3526
	Jurkat	Childhood T acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_0065
In Vivo Model	7.5×10⁶ HuT-102 tumor cells in 100 ul Media:Matrigel (1:1 ratio) were inoculated subcutaneously in the right flank of NOD/SCID mice (6-8 weeks, 20 g)
Result	Our combination model offers the possibility to use up to twofold lower doses of Dox against ATL while exhibiting the same cancer inhibitory effects.

Pair Name	Tanshinone IIA, Doxorubicin
Partner Name	Tanshinone IIA
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	CTNNB1	hsa1499
In Vitro Model	MCF-7(DOX/R)	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_C4M9
Result	Tan II A could be used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy.

Pair Name	Silibinin, Doxorubicin
Partner Name	Silibinin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Expression	CDC25C	hsa995
	Down-regulation	Activity	CDK1	hsa983
	Up-regulation	Expression	CHEK1	hsa1111
	Up-regulation	Expression	MS4A1	hsa931
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
In Vivo Model	An orthotopic rat model of HCC was used, in which subcutaneously injected Morris hepatoma (MH)-3924A cells (5×10⁶) in syngeneic ACI rats (Harlan, USA) led to formation of a subcutaneous tumor within 14 days.
Result	Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study

Pair Name	Shikonin, Doxorubicin
Partner Name	Shikonin
Disease Info	[ICD-11: 2B33.5]	Lymphoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	MTOR	hsa2475
	Down-regulation	Expression	MYC	hsa4609
	Down-regulation	Expression	PIK3CA	hsa5290
In Vitro Model	Raji	EBV-related Burkitt lymphoma	Homo sapiens (Human)	CVCL_0511
	Namalwa	EBV-related Burkitt lymphoma	Homo sapiens (Human)	CVCL_0067
In Vivo Model	For establishment of the xenograft, a mixture of 1×10⁷ Namalwa cells and PBS was injected subcutaneously in the right oxter of each mouse.
Result	These data suggest that shikonin may be an encouraging chemotherapeutic agent in the clinical treatment of BL.

Pair Name	Secoisolariciresinol, Doxorubicin
Partner Name	Secoisolariciresinol
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->P-gp inhibitor
In Vitro Model	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
Result	Our results suggest SECO as a novel P-gp inhibitor that can re-sensitize cancer cells during DOX chemotherapy.

Pair Name	Sclareol, Doxorubicin
Partner Name	Sclareol
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
Result	The developed SLN efficiently encapsulate DOX and SC and show good potential as an alternative for cancer treatment.

Pair Name	Sanguinarium, Doxorubicin
Partner Name	Sanguinarium
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CCND1	hsa595
	Up-regulation	Expression	CDKN1A	hsa1026
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	MCR-5	Healthy	Homo sapiens (Human)	CVCL_0440
Result	Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

Pair Name	Rhein, Doxorubicin
Partner Name	Rhein
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
In Vitro Model	SMMC-7721	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0534
	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	Our data indicate that a decline in mitochondrial energy metabolism was responsible for the synergistic antitumor effects of rhein and DOX in hepatocellular carcinoma cells. Reduction of ΔΨm and opening of mPTP inhibited the exchange of ATP/adenosine diphosphate between mitochondrial matrix and cytoplasm is the important mechanism.

Pair Name	RA-V, Doxorubicin
Partner Name	RA-V
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Biological Phenomena	Induction-->Mitochondria-mediated apoptosis
Gene Regulation	Up-regulation	Expression	CYCS	hsa54205
In Vitro Model	HeLa	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0030
In Vivo Model	The HeLa cells (5×10⁶ cells) were transplanted subcutaneously into the 8-week female BALB/c nude mice by using a stereotactic fixation device with mouse adaptor.
Result	This work represents a versatile strategy for precise combination therapy against resistant tumor with spatiotemporal control, and provides a potential tool for Cyt c-related apoptotic studies.

Pair Name	Quercetin, Doxorubicin
Partner Name	Quercetin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->ROS accumulation
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	MYC	hsa4609
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vivo Model	Into the right hind limb of each nude mouse, 2×10⁶ 4 T1 TNBC cells were injected subcutaneously. One week later, the mice were randomly divided into four groups (n = 3): control group (0.9% saline); Que group (50 mg/kg Que); AC group (5 mg/kg Dox plus 50 mg/kg Cyc); and AC plus Que group (5 mg/kg Dox plus 50 mg/kg Cyc plus 50 mg/kg Que).
Result	Que could attenuate AC-induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition,in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC

Pair Name	Quercetin, Doxorubicin
Partner Name	Quercetin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	These findings demonstrated that quercetin is important in MDR and may be developed into a new reversal agent for cancer chemotherapy.

Pair Name	Quercetin, Doxorubicin
Partner Name	Quercetin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	CASP9	hsa842
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
Result	These findings demonstrated that quercetin is important in MDR and may be developed into a new reversal agent for cancer chemotherapy.

Pair Name	Polyphyllin VI, Doxorubicin
Partner Name	Polyphyllin VI
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	MAP1LC3A	hsa84557
In Vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0248
Result	Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

Pair Name	Piperlongumine, Doxorubicin
Partner Name	Piperlongumine
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CDH2	hsa1000
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	CTNNB1	hsa1499
	Down-regulation	Expression	FN1	hsa2335
	Down-regulation	Expression	NFKB1	hsa4790
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	SMAD4	hsa4089
	Down-regulation	Expression	TNF	hsa7124
	Up-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	TWIST1	hsa7291
In Vitro Model	MG-63	Osteosarcoma	Homo sapiens (Human)	CVCL_0426
	143B	Osteosarcoma	Homo sapiens (Human)	CVCL_2270
	KHOS/NP	Osteosarcoma	Homo sapiens (Human)	CVCL_2546
Result	Piperlongumine induces ROS mediated apoptosis by transcriptional regulation of SMAD4/P21/P53 genes and synergizes with doxorubicin in osteosarcoma cells

Pair Name	Peiminine, Doxorubicin
Partner Name	Peiminine
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Gene Regulation	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	EGFR	hsa1956
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PTK2	hsa5747
In Vitro Model	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
Result	Our findings indicated that sinapine played an important role in the downregulation of MDR1 expression through suppression of fibroblast growth factor receptor (FGFR)4/FRS2α-ERK1/2 mediated NF-κB activation in MCF-7/dox cancer cells.

Pair Name	Palmatine, Doxorubicin
Partner Name	Palmatine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Proliferation
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	T-47D	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0553
	ZR75-1	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0588
Result	Our studies suggest that PLT can be a potential candidate agent for preventing and treating breast cancer.

Pair Name	Oleuropein, Doxorubicin
Partner Name	Oleuropein
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	NFKB1	hsa4790
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vivo Model	The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1),the volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease.
Result	The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.

Pair Name	Noscapine, Doxorubicin
Partner Name	Noscapine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	NFKBIA	hsa4792
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0419
In Vivo Model	For a xenograft model, 3×10⁶ MDA-MB-231 cells were inoculated subcutaneously into right flank of mice.
Result	Noscapine potentiated the anticancer activity of Doxorubicin in a synergistic manner against TNBC tumors via inactivation of NF-KB and anti-angiogenic pathways while stimulating apoptosis. These findings suggest potential benefit for use of oral Noscapine and Doxorubicin combination therapy for treatment of more aggressive TNBC.

Pair Name	Mangiferin, Doxorubicin
Partner Name	Mangiferin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in sub-G1 phase
Gene Regulation	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Down-regulation	Expression	NFKB1	hsa4790
	Up-regulation	Expression	PMAIP1	hsa5366
	Up-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	IM-9	Healthy	Homo sapiens (Human)	CVCL_1305
	RPMI-8226	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0014
Result	Our findings suggest that the combination of mangiferin and an anticancer drug could be used as a new regime for the treatment of MM.

Pair Name	Lycopene, Doxorubicin
Partner Name	Lycopene
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0419
Result	Our results thus show the therapeutic benefit of red guava extracts as a potential cancer treatment for TNBC in combination with doxorubicin or targeted therapy.

Pair Name	Isorhamnetin, Doxorubicin
Partner Name	Isorhamnetin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	MTOR	hsa2475
	Down-regulation	Expression	PRKAA1	hsa5562
	Down-regulation	Expression	RPS6KB1	hsa6198
In Vitro Model	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
In Vivo Model	a total of 0.1 ml of medium and Matrigel suspension containing 8×10⁷ MCF7/ADR cells was prepared for subcutaneous inoculation.
Result	Isorhamnetin induces cell cycle arrest and apoptosis by triggering DNA damage and regulating the AMPK/mTOR/p70S6K signaling pathway in doxorubicin-resistant breast cancer

Pair Name	Hyaluronic acid, Doxorubicin
Partner Name	Hyaluronic acid
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Immunomodulatory
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
In Vivo Model	Breast cancer xenograft mouse model was constructed by transplanting 4T1 cells subcutaneously to the nude mice and used in the following experiments at 10 d after inoculation
Result	This multifunctional nanoparticle system could deliver R848 and DOX respectively to tumor microenvironment and breast cancer cells to achieve synergistic effects of immunotherapy and chemotherapy against breast cancer.

Pair Name	Hesperetin, Doxorubicin
Partner Name	Hesperetin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Expression	ERBB2	hsa2064
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	RAC1	hsa5879
In Vitro Model	MCF-7/HER2-18	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_0U80
Result	These results indicated that the combination of Hst and Dox-induced cell cycle arrest, apoptosis, decreased HER2, Rac1, MMP9 expression, and cell migration. Thus, Hst may have the potential to be developed as a co-chemotherapeutic agent combined with doxorubicin toward HER2 overexpressing breast cancer cells.

Pair Name	Gossypol, Doxorubicin
Partner Name	Gossypol
Disease Info	[ICD-11: 2B5A]	Biphasic synovial sarcoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in S phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
In Vitro Model	SW982	Biphasic synovial sarcoma	Homo sapiens (Human)	CVCL_1734
Result	Combination therapy with L gossypol and low-concentration doxorubicin inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone

Pair Name	Glucosinalbate, Doxorubicin
Partner Name	Glucosinalbate
Disease Info	[ICD-11: 2C90]	Ehrlich ascites carcinoma		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Up-regulation	Expression	APAF1	hsa317
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	CASP9	hsa842
	Up-regulation	Expression	CYCS	hsa54205
	Up-regulation	Expression	GSTP1	hsa2950
	Up-regulation	Expression	HMOX1	hsa3162
	Down-regulation	Expression	IL6	hsa3569
	Down-regulation	Expression	KEAP1	hsa9817
	Up-regulation	Expression	LBR	hsa3930
	Down-regulation	Expression	MMP9	hsa4318
	Up-regulation	Expression	NFE2L2	hsa4780
	Up-regulation	Expression	NFKBIA	hsa4792
	Down-regulation	Expression	NOS2	hsa4843
	Up-regulation	Expression	NQO1	hsa1728
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PTGS2	hsa5743
	Down-regulation	Expression	RELA	hsa5970
	Down-regulation	Expression	VEGFA	hsa7422
In Vivo Model	Ehrlich ascites carcinoma cell was maintained in Swiss albino mice by weekly intraperitoneal transplantation of 1×10⁶ viable tumor cells suspended in isotonic phosphate-buffered solution (PBS).
Result	The present study clearly suggested therapeutic benefit of I3C in combination with DOX by augmenting anticancer efficacy and diminishing toxicity to the host.

Pair Name	Ginsenoside Rg3, Doxorubicin
Partner Name	Ginsenoside Rg3
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
In Vitro Model	143B	Osteosarcoma	Homo sapiens (Human)	CVCL_2270
	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
In Vivo Model	Ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models.
Result	We concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.

Pair Name	Ginsenoside Rg1, Doxorubicin
Partner Name	Ginsenoside Rg1
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	APAF1	hsa317
	Up-regulation	Expression	ATM	hsa472
	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP9	hsa842
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	H2AX	hsa3014
	Down-regulation	Expression	MAPK1	hsa5594
	Up-regulation	Expression	RAD51	hsa5888
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	TP53	hsa7157
	Up-regulation	Expression	XRCC1	hsa7515
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	The present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.

Pair Name	Ginger extract, Doxorubicin
Partner Name	Ginger extract
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	NFKB1	hsa4790
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Up-regulation	Expression	TP53	hsa7157
In Vivo Model	1×10⁶ EAC cells were implanted subcutaneously into the right thigh of the lower limb of mice.
Result	AMPK pathway and cyclin D1 gene expression could be a molecular therapeutic target for the anticancer effect of GE in mice bearing SEC. Combining GE and DOX revealed a greater efficacy as anticancer therapeutic regimen.

Pair Name	Gambogic Acid, Doxorubicin
Partner Name	Gambogic Acid
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	CDH13	hsa1012
	Up-regulation	Expression	FAS	hsa355
	Down-regulation	Expression	NFKBIA	hsa4792
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	RELA	hsa5970
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vivo Model	Viable A549 cells (5×10⁶/100 ul PBS per mouse) were mixed with 50% Matrigel, and then subcutaneously injected into the right flank of 7- to 8- week old male Balb/c nude mice.
Result	These findings indicate that GA sensitizes lung cancer cells to ADM in vitro and in vivo, providing a rationale for the combined use of GA and ADM in lung cancer chemotherapy.

Pair Name	Gambogenic acid, Doxorubicin
Partner Name	Gambogenic acid
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	MAP1LC3A	hsa84557
	Down-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	BEL-7402	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_5492
Result	Gambogenic Acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin.

Pair Name	Furanodiene, Doxorubicin
Partner Name	Furanodiene
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP7	hsa840
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	ESR1	hsa2099
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future.

Pair Name	Furanodiene, Doxorubicin
Partner Name	Furanodiene
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Cell metastasis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	CTNNB1	hsa1499
	Down-regulation	Expression	ITGAV	hsa3685
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Phosphorylation	PIK3R1	hsa5295
	Down-regulation	Phosphorylation	PTK2	hsa5747
	Down-regulation	Phosphorylation	PXN	hsa5829
	Down-regulation	Phosphorylation	SRC	hsa6714
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	These observations indicate that furanodiene is a potential agent that may be utilized to improve the anticancer efficacy of doxorubicin and overcome the risk of chemotherapy in highly metastatic breast cancer.

Pair Name	Fucoxanthin, Doxorubicin
Partner Name	Fucoxanthin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	ABCG2	hsa9429
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Down-regulation	Expression	CD9	hsa928
	Down-regulation	Activity	CYP3A4	hsa1576
	Down-regulation	Activity	GSTT1	hsa2952
	Up-regulation	Activity	TP53	hsa7157
In Vitro Model	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens (Human)	CVCL_0532
Result	The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes

Pair Name	Evodiamine, Doxorubicin
Partner Name	Evodiamine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC2	hsa329
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP7	hsa840
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	KRAS	hsa3845
	Down-regulation	Phosphorylation	MAP2K7	hsa5609
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Activity	PARP1	hsa142
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Our results indicated that EVO enhanced the apoptotic action of DOX by inhibiting the Ras/MEK/ERK cascade and the expression of IAPs without inhibiting the expression and activity of P-glycoprotein (P-gp). Taken together, our data indicate that EVO, a natural product, may be useful applied alone or in combination with DOX for the treatment of resistant breast cancer.

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Activity	DLL3	hsa10683
	Down-regulation	Activity	NOTCH3	hsa4854
	Down-regulation	Expression	SOX2-OT	KEGG ID N.A.
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens (Human)	CVCL_0548
In Vivo Model	1×10⁵ indicated cells were inoculated subcutaneously into the inguinal folds of NOD/SCID mice.
Result	SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Pair Name	Epifriedelanol, Doxorubicin
Partner Name	Epifriedelanol
Disease Info	[ICD-11: 2B33.2]	Chronic myeloid leukemia		Investigative
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	ABCC2	hsa1244
	Up-regulation	Expression	CXADR	hsa1525
	Up-regulation	Expression	NR1I2	hsa8856
In Vitro Model	K562/Adr	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_3827
Result	The present study demonstrated that Epi could enhance Adr-induced cytotoxicity towards K562/ADM cells accompanied by the down-regulation of P-gp and MRP2.

Pair Name	Emodin, Doxorubicin
Partner Name	Emodin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->DNA damage
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	PARP1	hsa142
	Down-regulation	Expression	RAD51	hsa5888
	Up-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	XRCC1	hsa7515
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Emodin Interferes With AKT1-Mediated DNA Damage and Decreases Resistance of Breast Cancer Cells to Doxorubicin

Pair Name	Dihydroartemisinin, Doxorubicin
Partner Name	Dihydroartemisinin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP7	hsa840
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	T-47D	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0553
Result	This study presented a new opportunity to enhance the effectiveness of future treatment regimens of breast cancer using DOX.

Pair Name	Dihydroartemisinin, Doxorubicin
Partner Name	Dihydroartemisinin
Disease Info	[ICD-11: 2A81]	Primary effusion lymphoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
In Vivo Model	An inhibitory effect on PEL growth was evaluated in a PEL-xenograft mouse model，DHA treatment also demonstrated an inhibitory effect on PEL cell growth in an in-vivo xenograft model.
Result	DHA is a potentially effective candidate drug for PEL treatment.

Pair Name	Decursin, Doxorubicin
Partner Name	Decursin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Phosphorylation	JAK2	hsa3717
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Activity	PTPN11	hsa5781
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
	Down-regulation	Phosphorylation	SRC	hsa6714
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	U266B1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0566
	RPMI-8226	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0014
	MM.1S	Plasma cell myeloma	Homo sapiens (Human)	CVCL_8792
Result	The combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

Pair Name	Damnacanthal, Doxorubicin
Partner Name	Damnacanthal
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP7	hsa840
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	ESR1	hsa2099
	Up-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

Pair Name	Curcumol, Doxorubicin
Partner Name	Curcumol
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	ABCC3	hsa8714
	Up-regulation	Expression	MIR181B2	KEGG ID N.A.
	Up-regulation	Activity	NFATC2	hsa4773
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vivo Model	MDA-MB-231-luc cells were suspended in a 1:1 mixture of saline/Matrigel and injected into the mammary fat pads of six-week-old female nude mice (n = 5 animals; 100 μL and 5×10⁶ cells per animal).
Result	Our study provides novel mechanistic evidence for curcumol-mediated sensitization to doxorubicin in TNBC, and it highlights the potential therapeutic usefulness of curcumol as an adjunct drug in TNBC patients with doxorubicin-resistance.

Pair Name	Curcumin, Doxorubicin
Partner Name	Curcumin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CDH1	hsa999
	Up-regulation	Expression	VIM	hsa7431
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
	H22	Hepatocellular carcinoma	Mus musculus (Mouse)	CVCL_H613
In Vivo Model	BALB/c mice were subcutaneously implanted with H22 cells at a concentration of 1×10⁶ cells per mouse.Therapeutic drugs (DOX, 3 mg/kg; CUR, 0.75 mg/kg) were injected into the mice in the treated groups (saline, DC, DOX/Pep2, DOX/Pep1, DC/Pep2, DC/Pep1) via the tail vein every other day for 14 days starting on day 6. The tumor sizes and mouse body weights were measured every other day.
Result	Our findings provide a novel and simple approach to nhibit the growth and metastasis of hepatocellular carcinoma.

Pair Name	Cucurbitacin B, Doxorubicin
Partner Name	Cucurbitacin B
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer		Investigative
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Expression	IREB2	hsa3658
	Up-regulation	Phosphorylation	MAPK3	hsa5595
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	8505C	Thyroid gland anaplastic carcinoma	Homo sapiens (Human)	CVCL_1054
	CAL-62	Thyroid gland anaplastic carcinoma	Homo sapiens (Human)	CVCL_1112
	8505C	Thyroid gland anaplastic carcinoma	Homo sapiens (Human)	CVCL_1054
	CAL-62	Thyroid gland anaplastic carcinoma	Homo sapiens (Human)	CVCL_1112
Result	Synergistic cytotoxicity of doxorubicin with cucurbitacin B is mediated by B-cell chronic lymphocytic leukemia/lymphoma 2 family proteins, survivin, and reactive oxygen species and modulated by Janus kinase 2/signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 in anaplastic thyroid carcinoma cells.

Pair Name	Costunolide, Doxorubicin
Partner Name	Costunolide
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Phosphorylation	MAPK14	hsa1432
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
In Vivo Model	PC-3 cells (3×10⁶) were injected subcutaneously into the armpit of each mouse.
Result	We suggested that costunolide in combination with doxorubicin was a new potential chemotherapeutic strategy for treating prostate cancer.

Pair Name	Costunolide, Doxorubicin
Partner Name	Costunolide
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
Result	These results demonstrate that costunolide may be a potent therapeutic agent against chronic myeloid leukemia.

Pair Name	Corilagin, Doxorubicin
Partner Name	Corilagin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
In Vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0326
Result	We speculate the possible use of corilagin in combination with low dosages of the anticancer chemotherapeutic standard drugs like cisplatin and doxorubicin, with the aim of obtaining an increment in the anticancer effect.

Pair Name	Chlorogenic acid, Doxorubicin
Partner Name	Chlorogenic acid
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	MAPK3	hsa5595
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
	MG-63	Osteosarcoma	Homo sapiens (Human)	CVCL_0426
Result	These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.

Pair Name	Chebulagic acid, Doxorubicin
Partner Name	Chebulagic acid
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Activity	MAPK1	hsa5594
	Down-regulation	Activity	MAPK14	hsa1432
	Down-regulation	Activity	MAPK8	hsa5599
	Down-regulation	Expression	NFKB1	hsa4790
	Down-regulation	Expression	PTGS2	hsa5743
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	The present study shows the efficacy of CA to overcome MDR-1 mediated drug resistance in HepG2 cells through COX-2 dependant modulation of MDR-1.

Pair Name	Camptothecin, Doxorubicin
Partner Name	Camptothecin
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Gene Regulation	Up-regulation	Expression	CTNNB1	hsa1499
In Vitro Model	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
	BT-474	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0179
In Vivo Model	Tumor inoculation was achieved by subcutaneously injecting 5×10⁴ 4T1 cells in the abdominal mammary gland of female BALB/c mice in order to prevent interference with normal bodily functions.
Result	Camptothecin-doxorubicin combinations showed synergistic antitumor acitivity.

Pair Name	Bufalin, Doxorubicin
Partner Name	Bufalin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	BID	hsa637
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
	HLE	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_1281
Result	These results suggested that the combination of cinobufacini and doxorubicin may provide a new strategy for inhibiting the proliferation of HCC cells.

Pair Name	Brassinolid, Doxorubicin
Partner Name	Brassinolid
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	APC	hsa324
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Down-regulation	Expression	JUN	hsa3725
	Down-regulation	Expression	MMP1	hsa4312
	Down-regulation	Expression	MMP26	hsa56547
	Down-regulation	Expression	MMP7	hsa4316
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	MYC	hsa4609
	Down-regulation	Expression	NANOG	hsa79923
	Up-regulation	Expression	POU5F1	hsa5460
	Down-regulation	Expression	SOX9	hsa6662
	Up-regulation	Expression	VEGFA	hsa7422
In Vitro Model	NCI-H69	Lung small cell carcinoma	Homo sapiens (Human)	CVCL_1579
Result	These data indicate that EB, a natural product with widespread occurrence in plants, is pharmacologically active in both drug-sensitive and drug-resistant SCLC cells and acts through the Wnt signaling pathway.

Pair Name	Betulinic Acid, Doxorubicin
Partner Name	Betulinic Acid
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Biological Phenomena	Induction-->ROS accumulation
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	U-937	Adult acute monocytic leukemia	Homo sapiens (Human)	CVCL_0007
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens (Human)	CVCL_2119
Result	Dox and the drug combination selectively reduced (p < 0.05) a recently reported anti-apoptotic Bcl-2 protein isoform p15-20-Bcl-2 in MOLM-13 by our group, without affecting the usually reported p26-Bcl-2-α.

Pair Name	Beta-Caryophyllene, Doxorubicin
Partner Name	Beta-Caryophyllene
Disease Info	[ICD-11: 2C17]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Phosphorylation	H2AX	hsa3014
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	Mz-ChA-1	Gallbladder carcinoma	Homo sapiens (Human)	CVCL_6932
Result	This evidence highlighted a possible role of STAT3 as a final effector of a complex network regulated by β-caryophyllene, which leads to an enhanced doxorubicin-sensitivity of cholangiocarcinoma cells and a lowered chemotherapy toxicity in nonmalignant cholangiocytes, thus strengthening the interest for this natural sesquiterpene as a dual-acting chemosensitizing and chemopreventive agent.

Pair Name	Baicalin, Doxorubicin
Partner Name	Baicalin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CYCS	hsa54205
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	This study demonstrate that the effect of baicalin on Dox treatment could enhance cytotoxicity toward breast cancer cells via the ROS/[Ca2+]i-mediated intrinsic apoptosis pathway-thus potentially lessening the required dosage of doxorubicin, and further exploring associated mechanisms in combined treatments for breast cancer clinical interventions in the future.

Pair Name	Baicalein, Doxorubicin
Partner Name	Baicalein
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Expression	CDK1	hsa983
	Down-regulation	Phosphorylation	DNM1L	hsa10059
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Expression	PINK1	hsa65018
	Down-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	Baicalein sensitizes triple negative breast cancer MDA-MB-231 cells to doxorubicin via autophagy-mediated down-regulation of CDK1

Pair Name	Apigenin, Doxorubicin
Partner Name	Apigenin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Inhibition-->Cell migration
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	CYCS	hsa54205
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
	Up-regulation	Expression	PSMD9	hsa5715
	Up-regulation	Expression	PTEN	hsa5728
	Down-regulation	Expression	SNAI1	hsa6615
	Down-regulation	Expression	TWIST1	hsa7291
In Vitro Model	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
Result	Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells

Pair Name	2,3,5,6-Tetramethylpyrazine, Doxorubicin
Partner Name	2,3,5,6-Tetramethylpyrazine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Mitochondria-mediated apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CCNA2	hsa890
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Expression	PIK3CA	hsa5290
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	K562/A02	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0368
Result	DLJ14 and Adr combination treatment may inhibit proliferation of Adr-resistant human breast cancer cells through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis via the mitochondrial-mediated apoptosis pathway.

Pair Name	Wogonin, Doxorubicin
Partner Name	Wogonin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	NFE2L2	hsa4780
In Vitro Model	MCF-7(DOX/R)	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_C4M9
Result	Wogonin reversed drug resistance and its reversal mechanism might be due to the suppression of Nrf2 signaling pathway, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs.

Pair Name	Voacamine, Doxorubicin
Partner Name	Voacamine
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Autophagy
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
	U-2 OS R1	Osteosarcoma	Homo sapiens (Human)	CVCL_T429
Result	Voacamine is capable of enhancing the cytotoxic effect of DOX on MDR cells by favouring a lethal autophagic process

Pair Name	Sinapine, Doxorubicin
Partner Name	Sinapine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	FOXP3	hsa50943
	Up-regulation	Expression	IL17A	hsa3605
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Our findings indicated that sinapine played an important role in the downregulation of MDR1 expression through suppression of fibroblast growth factor receptor (FGFR)4/FRS2α-ERK1/2 mediated NF-κB activation in MCF-7/dox cancer cells.

Pair Name	Sclareol, Doxorubicin
Partner Name	Sclareol
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
In Vivo Model	4T1 (2.5×10⁶) tumour cells were subcutaneously injected into the right thigh of female BALB/c mice (5 weeks old, around 20 g).
Result	This work shows that SC and DOX present synergistic anticancer activity for breast cancer treatment whereas NLC-DOX-SC was a feasible alternative to attain the benefits posed by DOX:SC combination but with none to fewer side effects.

Pair Name	Parthenolide, Doxorubicin
Partner Name	Parthenolide
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Overexpression of both Nrf2 and its target activities
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	HSPA4	hsa3308
	Down-regulation	Expression	NFE2L2	hsa4780
	Down-regulation	Expression	SOD2	hsa6648
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	PN prevented the acquisition of resistance induced by Mitox and DOX treatment in MDA-MB231 cells. This effect was mediated by inhibition of overexpression of both Nrf2 and its target activities. Therefore, within MDA-MB231 cell lines, PN not only exerts toxic effects on stem-like cells, which are responsible for tumour recurrence, but also prevents drug resistance

Pair Name	Guggulsterone, Doxorubicin
Partner Name	Guggulsterone
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	BCL2	hsa596
In Vitro Model	MCF-7(DOX/R)	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_C4M9
	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vivo Model	Transplantable cells (1×10⁷) were collected and subcutaneously injected in the right flanks of mice.
Result	Further studies demonstrated the inhibitory effects of guggulsterone on Bcl-2 and P-glycoprotein expression were the possible reason to increase chemosensitivity of MCF-7/DOX cells to doxorubicin in vivo. Examining body weight, hematological parameters, hepatic, cardiac and gastrointestinal tracts histopathology revealed that no significant signs of toxicity were related to guggulsterone. Guggulsterone might reverse doxorubicin resistance in vivo, with no severe side effects.

Pair Name	Gallic acid, Doxorubicin
Partner Name	Gallic acid
Disease Info	[ICD-11: 2B33.4]	Leukemia		Investigative
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
Result	GA enhanced the anticancer effect of Pira on K562 and K562/Dox cancer cells through cellular energy status impairment, and was able to reverse drug resistance in living K562/Dox cancer cells by inhibiting the function of P‑glycoprotein.

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Biological Phenomena	Induction-->Oxidative Stress
Gene Regulation	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	KB-A1	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_1D82
Result	These results demonstrate that the reversal effect of TP and EGCG on MDR acts, at least in part, regulating the doxorubicin induced intracellular concentration of ROS.

Pair Name	Decursin, Doxorubicin
Partner Name	Decursin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
Result	AGN would be a potentially novel treatment option for multidrug-resistant tumors by sensitizing to anticancer agents.

Pair Name	Caffeic acid phenethyl ester, Doxorubicin
Partner Name	Caffeic acid phenethyl ester
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Lipid metabolism
Gene Regulation	Down-regulation	Expression	ACACA	hsa31
	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	FASN	hsa2194
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Down-regulation	Expression	SCD	hsa6319
	Down-regulation	Expression	SREBF1	hsa6720
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Our results suggest that CAPE treatment reversed DOX resistance in breast cancer cells, at least in part by inhibiting Akt/mTOR/SREBP1 pathway-mediated lipid metabolism, indicating that CAPE may be an effective substance to assist in the treatment of breast cancer.

Pair Name	Aloe emodin, Doxorubicin
Partner Name	Aloe emodin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->DNA damage
Gene Regulation	Down-regulation	Activity	ABCB1	hsa5243
	Up-regulation	Cleavage	CASP3	hsa836
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Our study indicated that AE could be a potential reversal agent to resensitize ADR resistant in tumor chemotherapy and inhibiting autophagy might be an effective strategy to further enhance the reversal activity of AE.

Pair Name	Vanillin, Doxorubicin
Partner Name	Vanillin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP9	hsa842
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vivo Model	Mice were inoculated with 0.1 ml containing 5×10⁵ viable EAC cells/mice in the right hind limb (thigh) subcutaneously.
Result	Vanillin can be a potential lead molecule for the development of non-toxic agents for the treatment of breast cancer either alone or combined with DOX.

Pair Name	Tanshinone IIA, Doxorubicin
Partner Name	Tanshinone IIA
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	ABCC1	hsa4363
	Down-regulation	Expression	ABCG2	hsa9429
	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	PTEN	hsa5728
In Vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_0031
	MCF-7(DOX/R)	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_C4M9
In Vivo Model	2×10⁷ MCF‐7 cells were injected subcutaneously into the rightpostauricular region of each nude mouse.
Result	Tan IIA could be used as a novel agent combined with Dox in breast cancer therapy.

Pair Name	Sulforaphane, Doxorubicin
Partner Name	Sulforaphane
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Mitosis
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	MCF-10A	Healthy	Homo sapiens (Human)	CVCL_0598
In Vivo Model	The 2×10⁵ 4T1 cells from in vitro culture in 0.05 mL PBS were injected into the mammary fat pad.
Result	Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model

Pair Name	Oridonin, Doxorubicin
Partner Name	Oridonin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	SaOS-2	Osteosarcoma	Homo sapiens (Human)	CVCL_0548
Result	The combined use of oridonin and doxorubicin could help to reduce the clinical dosage of doxorubicin and its dangerous side effects.

Pair Name	Oridonin, Doxorubicin
Partner Name	Oridonin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Down-regulation	Expression	KDR	hsa3791
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vivo Model	A breast tumor xenograft model was established via subcutaneous flank inoculation of BALB/c female nude mice with 1×10⁶ MDA-MB-231 cells in 100 μl PBS containing 50% Matrigel per mouse.
Result	Our findings provide strong evidence that Ori may be highly promising in enhancing the efficacy of Dox and decreasing its adverse cardiotoxic effects, thus suggesting that Ori may serve as a potential adjunct therapy during Dox-based chemotherapy.

Pair Name	Oleanolic Acid, Doxorubicin
Partner Name	Oleanolic Acid
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	CASP9	hsa842
	Up-regulation	Expression	DIABLO	hsa56616
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	MRC-5	Healthy	Homo sapiens (Human)	CVCL_0440
Result	This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.

Pair Name	Magnoflorine, Doxorubicin
Partner Name	Magnoflorine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Phosphorylation	MAPK14	hsa1432
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
	Down-regulation	Expression	SQSTM1	hsa8878
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vivo Model	1×10⁷ MCF-7 cells suspended in 0.2 ml PBS were injected into the right flank of each mouse at a single site.
Result	Magnoflorine improves sensitivity to doxorubicin (DOX) of breast cancer cells via inducing apoptosis and autophagy through AKT/mTOR and p38 signaling pathways

Pair Name	Levistolide A, Doxorubicin
Partner Name	Levistolide A
Disease Info	[ICD-11: 2B33.2]	Chronic myeloid leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
In Vitro Model	K562/dox	Doxorubicin-resistant blast phase chronic myelogenous leukemia	Homo sapiens (Human)	N.A.
Result	Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway

Pair Name	Ginsenoside Rh2, Doxorubicin
Partner Name	Ginsenoside Rh2
Disease Info	[ICD-11:2D40]	Ehrlich's adenocarcinoma		Investigative
Gene Regulation	Up-regulation	Expression	NFE2L2	hsa4780
In Vivo Model	CD-1 albino mice were inoculated intraperitoneally (i.p.) with 0.5 mL PBS containing 3×10⁶ cells of Ehrlich’s adenocarcinoma (cells were derived from 7-day-old tumor re-transplanted into CD-1 mice).
Result	Rh2-induced direct activation of Nrf2 might provide additional benefits by minimizing DOX toxicity towards non-cancerous cells.

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Immunogenic cell death
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
In Vivo Model	About 1.0×10⁶ MCF-7/ADR cells were slowly injected into the subcutaneous region of male nude mice.
Result	PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

Pair Name	Aloin, Doxorubicin
Partner Name	Aloin
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Induction-->Oxidative Stress
Gene Regulation	Down-regulation	Expression	IL19	hsa29949
	Down-regulation	Expression	IL1B	hsa3553
	Down-regulation	Expression	IL6	hsa3569
	Down-regulation	Expression	TNF	hsa7124
In Vivo Model	Male Wistar rats (150-200 g, age 6-8 weeks) were used in this study.
Result	Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.

Pair Name	10-Gingerol, Doxorubicin
Partner Name	10-Gingerol
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Cell metastasis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Down-regulation	Expression	CDK1	hsa983
	Down-regulation	Expression	CDK2	hsa1017
	Down-regulation	Expression	CDK4	hsa1019
	Down-regulation	Expression	CDK6	hsa1021
	Up-regulation	Expression	H2AX	hsa3014
In Vitro Model	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
In Vivo Model	1×10⁶ human MDA-MB-231 HMTL.6 cells were injected into the inguinal mammary fat pad of Balb/c congenic athymic nude mice (40 µl/mouse in 50% matrigel, n = 6).
Result	Our data indicate that [10]-gingerol has potential to be used as a neoadjuvant or in combined therapy with doxorubicin, to improve its anticancer activity.