InterPAD - DETAILS

(+)-shikonin, (+-)-shikonin, (R)-(+)-shikonin, 1,4-naphthalenedione, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-, 1,4-naphthalenedione, 5,8-dihydroxy-2-((1r)-1-hydroxy-4-methyl-3-pentenyl)-, 1,4-naphthalenedione, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-, (R)-, 1,4-naphthoquinone, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-, (+)-, 2-((1R)-1-hydroxy-4-methyl-3-pentenyl)-5,8-dihydroxy-1,4-naphthoquinone, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-1,4-naphthalenedione, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-1,4-naphthalenedione, isoarnebin 4, shikonin, shikonin, (+)-isomer

No.	Title	Href
1	Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo. Chin Med. 2020 Mar 10;15:23. doi: 10.1186/s13020-020-00305-1.	`Click`
2	Shikonin potentiates therapeutic efficacy of oxaliplatin through reactive oxygen species-mediated intrinsic apoptosis and endoplasmic reticulum stress in oxaliplatin-resistant colorectal cancer cells. Drug Dev Res. 2023 May;84(3):542-555. doi: 10.1002/ddr.22044.	`Click`
3	Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway. Life Sci. 2018 Jul 1;204:71-77. doi: 10.1016/j.lfs.2018.05.012.	`Click`
4	Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin. Sci Rep. 2018 Feb 20;8(1):3317. doi: 10.1038/s41598-018-21570-z.	`Click`
5	Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo. Biochem Biophys Res Commun. 2016 Jan 22;469(4):1075-82. doi: 10.1016/j.bbrc.2015.12.100.	`Click`
6	Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol (Dordr). 2017 Jun;40(3):247-261. doi: 10.1007/s13402-017-0320-1.	`Click`
7	Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer. 2015 Sep 15;137(6):1446-56. doi: 10.1002/ijc.29483.	`Click`
8	A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Phytomedicine. 2020 Mar;68:153189. doi: 10.1016/j.phymed.2020.153189.	`Click`
9	Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways. BMC Cell Biol. 2018 Dec 29;19(1):29. doi: 10.1186/s12860-018-0179-7.	`Click`
10	Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33. doi: 10.1016/j.bcp.2014.01.041.	`Click`
11	Identification of a synergistic combination of dimethylaminoparthenolide and shikonin alters metabolism and inhibits proliferation of pediatric precursor-B cell acute lymphoblastic leukemia. Mol Carcinog. 2020 Apr;59(4):399-411. doi: 10.1002/mc.23163.	`Click`
12	Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation. Mol Biol Rep. 2024 Jan 6;51(1):86. doi: 10.1007/s11033-023-09056-2.	`Click`
13	Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor. Int J Mol Sci. 2024 Jan 3;25(1):616. doi: 10.3390/ijms25010616.	`Click`
14	Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. Phytomedicine. 2023 Apr;112:154701. doi: 10.1016/j.phymed.2023.154701.	`Click`
15	Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol Res. 2017;115:45-55. doi:10.1016/j.phrs.2016.11.011	`Click`
16	Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect. Phytomedicine. 2024 Jan;123:155214. doi: 10.1016/j.phymed.2023.155214.	`Click`

No.

Title

Href

Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo. Chin Med. 2020 Mar 10;15:23. doi: 10.1186/s13020-020-00305-1.

Click

Shikonin potentiates therapeutic efficacy of oxaliplatin through reactive oxygen species-mediated intrinsic apoptosis and endoplasmic reticulum stress in oxaliplatin-resistant colorectal cancer cells. Drug Dev Res. 2023 May;84(3):542-555. doi: 10.1002/ddr.22044.

Click

Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway. Life Sci. 2018 Jul 1;204:71-77. doi: 10.1016/j.lfs.2018.05.012.

Click

Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin. Sci Rep. 2018 Feb 20;8(1):3317. doi: 10.1038/s41598-018-21570-z.

Click

Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo. Biochem Biophys Res Commun. 2016 Jan 22;469(4):1075-82. doi: 10.1016/j.bbrc.2015.12.100.

Click

Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol (Dordr). 2017 Jun;40(3):247-261. doi: 10.1007/s13402-017-0320-1.

Click

Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer. 2015 Sep 15;137(6):1446-56. doi: 10.1002/ijc.29483.

Click

A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Phytomedicine. 2020 Mar;68:153189. doi: 10.1016/j.phymed.2020.153189.

Click

Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways. BMC Cell Biol. 2018 Dec 29;19(1):29. doi: 10.1186/s12860-018-0179-7.

Click

Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33. doi: 10.1016/j.bcp.2014.01.041.

Click

Identification of a synergistic combination of dimethylaminoparthenolide and shikonin alters metabolism and inhibits proliferation of pediatric precursor-B cell acute lymphoblastic leukemia. Mol Carcinog. 2020 Apr;59(4):399-411. doi: 10.1002/mc.23163.

Click

Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation. Mol Biol Rep. 2024 Jan 6;51(1):86. doi: 10.1007/s11033-023-09056-2.

Click

Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor. Int J Mol Sci. 2024 Jan 3;25(1):616. doi: 10.3390/ijms25010616.

Click

Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. Phytomedicine. 2023 Apr;112:154701. doi: 10.1016/j.phymed.2023.154701.

Click

Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol Res. 2017;115:45-55. doi:10.1016/j.phrs.2016.11.011

Click

Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect. Phytomedicine. 2024 Jan;123:155214. doi: 10.1016/j.phymed.2023.155214.

Click

Name	Shikonin
PubChem CID	479503
Molecular Weight	288.29g/mol
Synonyms	(+)-shikonin, (+-)-shikonin, (R)-(+)-shikonin, 1,4-naphthalenedione, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-, 1,4-naphthalenedione, 5,8-dihydroxy-2-((1r)-1-hydroxy-4-methyl-3-pentenyl)-, 1,4-naphthalenedione, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-, (R)-, 1,4-naphthoquinone, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-, (+)-, 2-((1R)-1-hydroxy-4-methyl-3-pentenyl)-5,8-dihydroxy-1,4-naphthoquinone, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-1,4-naphthalenedione, 5,8-dihydroxy-2-(1-hydroxy-4-methyl-3-pentenyl)-1,4-naphthalenedione, isoarnebin 4, shikonin, shikonin, (+)-isomer
Formula	C₁₆H₁₆O₅
SMILES	CC(=CCC(C1=CC(=O)C2=C(C=CC(=C2C1=O)O)O)O)C
InChI	1S/C16H16O5/c1-8(2)3-4-10(17)9-7-13(20)14-11(18)5-6-12(19)15(14)16(9)21/h3,5-7,10,17-19H,4H2,1-2H3/t10-/m1/s1
InChIKey	NEZONWMXZKDMKF-SNVBAGLBSA-N
CAS Number	517-89-5
ChEMBL ID	CHEMBL9470
ChEBI ID	CHEBI:81068
Herb ID	HBIN043899
KEGG ID	C17412
Toxicity	Organism	Test Type	Route(Dose)
	rat	LD50	intraperitoneal(165 mg/kg)
	mouse	LD50	intraperitoneal(254 mg/kg)
	rat	LD50	oral(322 mg/kg)
Structure			Download 2D MOL 3D MOL

Chineses Pinyin	DianZiCao
Use Part	Root, Root Cortex
Habitat	SiChuan, GuiZhou, YunNan, XiZang, ChongQing, Shaanxi, GanSu, QingHai, NingXia, XinJiang

Chineses Pinyin	ZiCao
Use Part	Root
Habitat	YunNan, XiZang, SiChuan, GuiZhou
Flavor	Sweet, Salty
Meridian Tropism	Heart, Liver
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Boraginales 　　　　-->Family: Boraginaceae 　　　　　-->Genus: Arnebia 　　　　　　-->Species: Arnebia euchroma

Chineses Pinyin	BaiGuoZiCao
Use Part	Whole Herb
Habitat	LiaoNing, HuNan, HuBei, XinJiang
Flavor	Bitter
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Boraginales 　　　　-->Family: Boraginaceae 　　　　　-->Genus: Lithospermum 　　　　　　-->Species: Lithospermum officinale

Chineses Pinyin	MaoYeXiangChaCai
Use Part	Leaf
Habitat	JiangSu, HeNan, SiChuan, GuiZhou, YunNan, XiZang, ChongQing, GanSu
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Lamiales 　　　　-->Family: Lamiaceae 　　　　　-->Genus: Isodon 　　　　　　-->Species: Isodon japonicus

Chineses Pinyin	NeiMengZiCao
Habitat	XiZang, XinJiang, GanSu, NingXia, NeiMengGu, HeBei, Mongolia
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Boraginales 　　　　-->Family: Boraginaceae 　　　　　-->Genus: Arnebia 　　　　　　-->Species: Arnebia guttata

Chineses Pinyin	RuanZiCao
Use Part	Root
Habitat	Mediterranean
Flavor	Bitter
Meridian Tropism	Pericardium, Liver

Pair Name	Shikonin, 4-hydroxytamoxifen
Partner Name	4-hydroxytamoxifen
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BID	hsa637
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	DIABLO	hsa56616
	Up-regulation	Expression	FAS	hsa355
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PIK3CA	hsa5290
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vitro Model	MDA-MB-435S	Amelanotic melanoma	Homo sapiens (Human)	CVCL_0622
In Vivo Model	Portions of the suspension (6×10⁶ cells in 0.1 mL) were subcutaneously injected into the right flanks of each mouse.
Result	The combination of SK and 4-OHT shows highly efficient anticancer effects on breast cancer therapy. SK may be a promising candidate as an adjuvant to 4-OHT for breast cancer treatments, especially for ER- breast cancer.

Pair Name	Shikonin, Oxaliplatin
Partner Name	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	Our findings imply the potential of SHI to boost the sensitivity of OXA to CRC, offering promising benefits for clinical strategies to combat OXA resistance.

Pair Name	Shikonin, Gefitinib
Partner Name	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	PKM	hsa5315
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vivo Model	Mice were injected with A549 (1×10⁷) in the dorsal area.
Result	These results provide a promising therapeutic approach for the treatment of wild-type EGFR non-small cell lung cancer.

Pair Name	Shikonin, Doxorubicin
Partner Name	Doxorubicin
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
In Vitro Model	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	Shikonin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Biological Phenomena	Induction-->ROS generation; Induction--> Loss of mitochondrial membrane potential
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP9	hsa842
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
	SW620	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0547
	NCM460	Healthy	Homo sapiens (Human)	CVCL_0460
In Vivo Model	HCT116 cells (5×10⁶ cells in 100uL of PBS) were harvested and injected subcutaneously into the right flank of five-week-old athymic BALB/cA nu/nu female mice
Result	Shikonin as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by inducing intracellular oxidative stress

Pair Name	Shikonin, Temozolomide
Partner Name	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Inhibition-->Epithelial-mesenchymal transition
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	MMP2	hsa4313
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	SNAI2	hsa6591
	Down-regulation	Expression	VIM	hsa7431
In Vitro Model	U-118MG	Astrocytoma	Homo sapiens (Human)	CVCL_0633
Result	From our results we conclude that dual treatment with SHK and TMZ may constitute a powerful new tool for GBM treatment by reducing therapy resistance and tumor recurrence.

Pair Name	Shikonin, Erlotinib
Partner Name	Erlotinib
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	PLCG1	hsa5335
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	DK-MG	Glioblastoma	Homo sapiens (Human)	CVCL_1173
	SNB-19	Astrocytoma	Homo sapiens (Human)	CVCL_0535
	BS153	Glioblastoma	Homo sapiens (Human)	CVCL_S444
	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	T98G	Glioblastoma	Homo sapiens (Human)	CVCL_0556
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib.

Pair Name	Shikonin, Osimertinib
Partner Name	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	InductionROS generation
Gene Regulation	Up-regulation	Expression	ATF4	hsa468
Gene Regulation	Up-regulation	Phosphorylation	EIF2S1	hsa1965
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
Result	Shikonin increased the anticancer activity of AZD9291 in primary wtEGFR NSCLC cells through ROS-mediated ER stress

Pair Name	Shikonin, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Expression	BID	hsa637
	Down-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CASP8	hsa841
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Down-regulation	Expression	MCL1	hsa4170
	Down-regulation	Phosphorylation	STAT3	hsa6774
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	The results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.

Pair Name	Shikonin, Gemcitabine
Partner Name	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Activity	CDH13	hsa1012
	Down-regulation	Expression	COX2	hsa4513
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	MYC	hsa4609
	Down-regulation	Expression	VEGFA	hsa7422
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0152
In Vivo Model	Tumors were established by subcutaneous injection of 5×10⁶ BxPC-3 cells into the flanks of male nude BALB/c mice.
Result	Our results suggest that shikonin can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of gemcitabine through the suppression of NF-κB and NF-κB-regulated gene products.

Pair Name	Shikonin, Dimethylaminoparthenolide
Partner Name	Dimethylaminoparthenolide
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	FN1	hsa2335
In Vitro Model	Kasumi-2	Childhood B acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_0590
	KOPN-8	Childhood B acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_1866
	NALM-6	Adult B acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_0092
	RCH-ACV	Childhood B acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_1851
	Reh	Childhood B acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_1650
Result	This approach demonstrates that a synergistic pair of compounds with malignant cell specificity can effectively target metabolic pathways crucial to leukemia cell proliferation and induce apoptosis.

Pair Name	Shikonin, Anti-mouse PD-1
Partner Name	Anti-mouse PD-1
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Gene Regulation	Down-regulation	Expression	CALR	hsa811
	Down-regulation	Expression	HMGB1	hsa3146
	Up-regulation	Expression	HSPA4	hsa3308
In Vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_7254
In Vivo Model	6×10⁵ CT26 cells were subcutaneously inoculated into BALB/c mice in the right inguinal region.
Result	Our study elucidated the potential role of 'Shikonin-PKM2-ROS-Hsp70' axis in the promotion of efficacy of PD-1 blockade in CRC treatments, providing a potential strategy and targets for improving the efficacy of PD-1 blockade in colorectal cancer.

Pair Name	Shikonin, BEZ235
Partner Name	BEZ235
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	CD44	hsa960
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Down-regulation	Expression	NANOG	hsa79923
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	POU5F1	hsa5460
	Down-regulation	Expression	PROM1	hsa8842
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	We found that low doses shikonin and dual PI3K-mTOR inhibitor (BEZ235) have a synergistic effect that inhibits the spheroid formation from chemoresistant lung cancer sublines. Inhibiting the proliferation of lung cancer stem cells is believed to reduce the recurrence of lung cancer; therefore, shikonin's anti-drug resistance and anti-cancer stem cell activities make it a highly interesting molecule for future combined lung cancer therapy.