Pair Name	Tubeimoside I, TNF-related apoptosis inducing ligand
Partner Name	Tubeimoside I
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	CFLAR	hsa8837
	Down-regulation	Expression	STAMBPL1	hsa57559
In Vitro Model	Caki-1	Clear cell renal cell carcinoma	Homo sapiens (Human)	CVCL_0234
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	HeLa	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0030
	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
In Vivo Model	Male SCID mice were inoculated subcutaneously at the flank with HCT116 (5×10⁶) cells.
Result	Our study revealed that STAMBPL1 is essential for c-FLIP stabilization, and that STAMBPL1 depletion enhances TRAIL-mediated apoptosis via c-FLIP downregulation.

Pair Name	Thymoquinone, TNF-related apoptosis inducing ligand
Partner Name	Thymoquinone
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->ROS-mediated apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
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	The synergistic influence between TQ which induced the DR5 and TRAIL, facilitating the connection between TRAIL and its receptors on the cancerous cell membrane. Hence, the proposed combination therapy induced the ROS-mediated apoptotic stimulus.

Pair Name	Tanshinone IIA, TNF-related apoptosis inducing ligand
Partner Name	Tanshinone IIA
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	STAT3	hsa6774
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
In Vivo Model	Each mouse was injected subcutaneously with 0.2 mL of U87 cells (1×10⁵ cells/ml) at the hind limb.
Result	T-IIA increases TRAIL-induced apoptosis by downregulating STAT3 and upregulating DR4 and DR5, indicating T-IIA therapy as a novel treatment strategy for TRAIL-resistant GBM.

Pair Name	Sulforaphane, TNF-related apoptosis inducing ligand
Partner Name	Sulforaphane
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Up-regulation	Expression	BAK1	hsa578
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	CDH13	hsa1012
	Down-regulation	Expression	CDK1	hsa983
In Vitro Model	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
In Vivo Model	Mice were inoculated with PC-3 cells (1×10⁶ per 100 AL medium) into the dorsolateral lobe of the prostatic capsule.
Result	The ability of sulforaphane to inhibit tumor growth, metastasis, and angiogenesis and to enhance the therapeutic potential of TRAIL suggests that sulforaphane alone or in combination with TRAIL can be used for the management of prostate cancer.

Pair Name	Shikonin, TNF-related apoptosis inducing ligand
Partner Name	Shikonin
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	Resveratrol, TNF-related apoptosis inducing ligand
Partner Name	Resveratrol
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	786-O	Renal cell carcinoma	Homo sapiens (Human)	CVCL_1051
	OS-RC-2	Clear cell renal cell carcinoma	Homo sapiens (Human)	CVCL_1626
In Vivo Model	These data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice.
Result	Our data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice. These results suggest the possibility of a new combination therapeutic leading to the improvement of RCC treatment.

Pair Name	Pterostilbene, TNF-related apoptosis inducing ligand
Partner Name	Pterostilbene
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Up-regulation	Activity	DDIT3	hsa1649
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	BT-20	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_0178
Result	Pterostilbene enhances TRAIL-induced apoptosis through the induction of death receptors and downregulation of cell survival proteins in TRAIL-resistance triple negative breast cancer cells

Pair Name	Periplocin, TNF-related apoptosis inducing ligand
Partner Name	Periplocin
Disease Info	[ICD-11: 2B70.1]	Esophageal squamous cell carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Down-regulation	Activity	CTNNB1	hsa1499
	Down-regulation	Phosphorylation	CTNNB1	hsa1499
	Down-regulation	Activity	FOXP3	hsa50943
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_6898
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_1759
	YES-2	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_E322
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_1351
	KYSE-410	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_1352
	KYSE-510	Esophageal squamous cell carcinoma	Homo sapiens (Human)	CVCL_1354
Result	Our data suggest that CPP and TRAIL could be further explored as potential therapeutic approach for esophageal cancer.

Pair Name	Periplocin, TNF-related apoptosis inducing ligand
Partner Name	Periplocin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BID	hsa637
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	EGR1	hsa1958
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Expression	MCL1	hsa4170
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vivo Model	The proceduresusing animals were approved by the Animal Care and Use Committee.SGC-7901 cells (1×10⁵/100μL/mouse) were suspended in 0.9%physiological saline and subcutaneously injected into the right flank ofeach mouse.
Result	Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway

Pair Name	Neobavaisoflavone, TNF-related apoptosis inducing ligand
Partner Name	Neobavaisoflavone
Disease Info	[ICD-11: 2F7Z]	Glioma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Cleavage	BID	hsa637
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	U-373MG ATCC	Astrocytoma	Homo sapiens (Human)	CVCL_2219
Result	Taken together, our results suggest that NBIF reduces the resistance of cancer cells to TRAIL and that the combination of NBIF and TRAIL may be a new therapeutic strategy for treating TRAIL-resistant glioma cells.

Pair Name	Medicarpin, TNF-related apoptosis inducing ligand
Partner Name	Medicarpin
Disease Info	[ICD-11: 2B33.1]	Myeloid leukemia		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	BCL-xL	hsa598
	Up-regulation	Expression	BID	hsa637
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP7	hsa840
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	CYCS	hsa54205
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Expression	DIABLO	hsa56616
	Down-regulation	Expression	DIABLO	hsa56616
	Up-regulation	Phosphorylation	EIF2S1	hsa1965
	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
	LAMA-84	Chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0388
	U-937	Adult acute monocytic leukemia	Homo sapiens (Human)	CVCL_0007
	OCI-AML-3	Adult acute myeloid leukemia	Homo sapiens (Human)	CVCL_1844
Result	Medicarpin, a legume phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the induction of DR5 and activation of the ROS-JNK-CHOP pathway

Pair Name	Luteolin, TNF-related apoptosis inducing ligand
Partner Name	Luteolin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Mitochondrial fission and apoptosis
Gene Regulation	Up-regulation	Expression	DNM1L	hsa10059
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
Result	TRAIL combined with luteolin could be as an effective chemotherapeutic strategy for NSCLC.

Pair Name	Luteolin, TNF-related apoptosis inducing ligand
Partner Name	Luteolin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vivo Model	A549 non-small cell lung cancer cells (2×10⁶) resuspended in 0.1mL of PBS were injected subcutaneously into athymic (nu/nu) male nude mice (5-6 weeks old).
Result	Data from this study thus provide strong in vivo evidence supporting that luteolin is a potential sensitizer for TRAIL in anticancer therapy.

Pair Name	Luteolin, TNF-related apoptosis inducing ligand
Partner Name	Luteolin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Gene Regulation	Down-regulation	Expression	CASP8	hsa841
	Down-regulation	Expression	MIR301A	hsa407027
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
Result	Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.

Pair Name	Liquiritin, TNF-related apoptosis inducing ligand
Partner Name	Liquiritin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CDH2	hsa1000
	Up-regulation	Expression	FADD	hsa8772
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	TWIST1	hsa7291
	Down-regulation	Expression	VIM	hsa7431
In Vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens (Human)	CVCL_0139
	SNU-216	Gastric tubular adenocarcinoma	Homo sapiens (Human)	CVCL_3946
Result	Combining TRAIL and liquiritin exerts synergistic effects against human gastric cancer cells and xenograft in nude mice through potentiating apoptosis and ROS generation

Pair Name	Licochalcone B, TNF-related apoptosis inducing ligand
Partner Name	Licochalcone B
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Phosphorylation	ATM	hsa472
	Up-regulation	Cleavage	CASP8	hsa841
	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Phosphorylation	CDK1	hsa983
	Down-regulation	Expression	CDK1	hsa983
	Up-regulation	Phosphorylation	CHEK2	hsa11200
	Up-regulation	Expression	DDIT3	hsa1649
	Down-regulation	Expression	EIF2AK3	hsa9451
	Up-regulation	Expression	H2AX	hsa3014
	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Phosphorylation	MAPK14	hsa1432
	Up-regulation	Phosphorylation	MAPK3	hsa5595
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Phosphorylation	MAPK9	hsa5601
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	PSMD9	hsa5715
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
Result	LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Pair Name	Kurarinone, TNF-related apoptosis inducing ligand
Partner Name	Kurarinone
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCNA2	hsa890
	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	CFLAR	hsa8837
	Down-regulation	Expression	MCL1	hsa4170
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	STAT3	hsa6774
In Vitro Model	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
Result	Kurarinone Synergizes TRAIL-Induced Apoptosis in Gastric Cancer Cells

Pair Name	Kaempferol, TNF-related apoptosis inducing ligand
Partner Name	Kaempferol
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	SW480	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0546
Result	The co-treatment induced no apoptosis in normal human peripheral blood mononuclear cells and little apoptosis in normal human hepatocytes. These results suggest that kaempferol is useful for TRAIL-based treatments for cancer.

Pair Name	Kaempferol, TNF-related apoptosis inducing ligand
Partner Name	Kaempferol
Disease Info	[ICD-11: 2A20.1]	Chronic myelogenous leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC2	hsa329
	Down-regulation	Expression	BIRC3	hsa330
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
Result	It is reasonable to conclude that sensitization of chronic leukemia cells to TRAIL by kaempferol in vitro should be considered as a way of focusing clinical attention on leukemia therapy.

Pair Name	Isoquercitrin, TNF-related apoptosis inducing ligand
Partner Name	Isoquercitrin
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	SiHa	Human papillomavirus-related cervical squamous cell carcinoma	Homo sapiens (Human)	CVCL_0032
Result	We found that isoquercitrin enhances the mRNA expression of TRAIL-Rs, but the percentage of apoptosis was meager, possibly due to the influence of other anti-apoptotic proteins.

Pair Name	Isoliquiritigenin, TNF-related apoptosis inducing ligand
Partner Name	Isoliquiritigenin
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis and autophagy
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
Result	Isoliquiritigenin has the potential to overcome resistance to TRAIL in cancer cells and its chemopreventive effects may depend on TRAIL function

Pair Name	Irigenin, TNF-related apoptosis inducing ligand
Partner Name	Irigenin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	FADD	hsa8772
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	NCI-N87	Gastric tubular adenocarcinoma	Homo sapiens (Human)	CVCL_1603
	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
	BGC-823	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_3360
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens (Human)	CVCL_5334
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens (Human)	CVCL_1416
Result	Our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment.

Pair Name	Icaritin, TNF-related apoptosis inducing ligand
Partner Name	Icaritin
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	RELA	hsa5970
In Vitro Model	U-373MG ATCC	Astrocytoma	Homo sapiens (Human)	CVCL_2219
	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
Result	These data suggest that icaritin sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent c-FLIP expression, providing in vitro evidence supporting the notion that icaritin is a potential sensitizer of TRAIL in anticancer therapy against human GBM.

Pair Name	Gomisin N, TNF-related apoptosis inducing ligand
Partner Name	Gomisin N
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HeLa	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0030
Result	Our results indicated that gomisin N was able to potentiate TRAIL-induced apoptosis through ROS-mediated up-regulation of DR4 and DR5.

Pair Name	Gambogic Acid, TNF-related apoptosis inducing ligand
Partner Name	Gambogic Acid
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BID	hsa637
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP7	hsa840
	Up-regulation	Cleavage	CASP8	hsa841
	Down-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	XIAP	hsa331
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
Result	These findings may open a new window in the treatment of breast cancer using TRAIL in combination with GA.

Pair Name	Fucoxanthin, TNF-related apoptosis inducing ligand
Partner Name	Fucoxanthin
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
In Vitro Model	Ca Ski	Human papillomavirus-related cervical squamous cell carcinoma	Homo sapiens (Human)	CVCL_1100
In Vivo Model	Five-week-old nude BALB/c mice were used for subcutaneous implantation of human cervical tumor cells HeLa (2×10⁶ per site).
Result	The findings of this study suggest that the combined use of fucoxanthin and TRAIL might be a useful strategy against TRAIL-resistant cervical cancer.

Pair Name	Fucoxanthin, TNF-related apoptosis inducing ligand
Partner Name	Fucoxanthin
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	RELA	hsa5970
In Vitro Model	HeLa	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0030
	SiHa	Human papillomavirus-related cervical squamous cell carcinoma	Homo sapiens (Human)	CVCL_0032
	Ca Ski	Human papillomavirus-related cervical squamous cell carcinoma	Homo sapiens (Human)	CVCL_1100
Result	We found that fucoxanthin- or TRAIL-induced apoptosis of human cervical cancer cells was obviously down-regulated. CONCLUSIONS Taken together, these findings suggest that fucoxanthin and TRAIL increased the apoptosis in human cervical cancer cells by targeting the PI3K/Akt/NF-κB signaling pathway.

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	PEA15	hsa8682
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Expression	TNFRSF10A	hsa8797
In Vitro Model	A-375	Amelanotic melanoma	Homo sapiens (Human)	CVCL_0132
Result	EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
In Vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0428
Result	Combination of epigallocatechin-3-gallate and TRAIL synergistically increase the apoptosis and cleavage of procaspase-3 in pancreatic cancer cells

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2B6B]	Nasopharyngeal carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	CDH13	hsa1012
	Down-regulation	Expression	CFLAR	hsa8837
	Down-regulation	Expression	FADD	hsa8772
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	CNE-1	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_6889
	C666-1	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_7949
	NP69SV40T	Healthy	Homo sapiens (Human)	CVCL_F755
Result	EGCG sensitizes NPC cells to TRAIL-mediated apoptosis via modulation of extrinsic and intrinsic apoptotic pathways and inhibition of NF-κB activation.

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ANGPT1	hsa284
	Down-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC3	hsa330
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CASP6	hsa839
	Down-regulation	Expression	CASP8	hsa841
	Down-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	MMP2	hsa4313
	Down-regulation	Expression	MMP3	hsa4314
	Down-regulation	Expression	MMP9	hsa4318
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PARP1	hsa142
	Up-regulation	Expression	TIMP1	hsa7076
	Down-regulation	Expression	VEGFA	hsa7422
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
Result	EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

Pair Name	Decursin, TNF-related apoptosis inducing ligand
Partner Name	Decursin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Activity	ATF4	hsa468
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Activity	EIF2AK3	hsa9451
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens (Human)	CVCL_1571
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
	Calu-1	Lung squamous cell carcinoma	Homo sapiens (Human)	CVCL_0608
Result	ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL-resistant NSCLC cell lines, partly via up-regulation of DR5.

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Partner Name	Curcumin
Disease Info	[ICD-11: 2C17]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Oxidative Stress-dependent apoptosis
Gene Regulation	Down-regulation	Expression	BIRC2	hsa329
	Up-regulation	Cleavage	CASP8	hsa841
	Down-regulation	Expression	CCR6	hsa1235
	Down-regulation	Expression	DDX3X	hsa1654
	Down-regulation	Expression	GSK3B	hsa2932
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HuCCA-1	Intrahepatic cholangiocarcinoma	Homo sapiens (Human)	CVCL_M255
	KKU-213A	Intrahepatic cholangiocarcinoma	Homo sapiens (Human)	CVCL_M261
Result	The present study demonstrates the potential of using curcumin in combination with TRAIL to yield better TRAIL therapy outcomes in TRAIL-resistant CCA.

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Partner Name	Curcumin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->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	CDH13	hsa1012
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Phosphorylation	MAPK3	hsa5595
	Down-regulation	Expression	MMP2	hsa4313
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Activity	NFKB1	hsa4790
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. The synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-kappaB via inhibition of the Akt/IKKalpha pathway and enhanced ERK1/2 activity

Pair Name	Chicoric acid, TNF-related apoptosis inducing ligand
Partner Name	Chicoric acid
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Down-regulation	Expression	MAP2K7	hsa5609
	Up-regulation	Activity	MAPK8	hsa5599
	Down-regulation	Expression	TIPRL	hsa261726
In Vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0336
Result	Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy.

Pair Name	Celastrol, TNF-related apoptosis inducing ligand
Partner Name	Celastrol
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
	LN-229	Glioblastoma	Homo sapiens (Human)	CVCL_0393
Result	The results of our study demonstrate that celastrol sensitizes glioma cells to TRAIL via the death receptor pathway and that DR5 plays an important role in the effects of this cotreatment. The results indicate that this cotreatment is a promising tumor-killing therapeutic strategy with high efficacy and low toxicity.

Pair Name	Celastrol, TNF-related apoptosis inducing ligand
Partner Name	Celastrol
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Expression	MAP1LC3A	hsa84557
	Up-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	HCC15	Lung squamous cell carcinoma	Homo sapiens (Human)	CVCL_2057
	Calu-3	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0609
Result	The combined use of TRAIL with celastrol may serve as a safe and adequate therapeutic technique for the treatment of TRAIL‑resistant lung cancer, suggesting that celastrol‑mediated autophagy flux inhibition sensitized TRAIL‑initiated apoptosis via regulation of ROS and ΔΨm.

Pair Name	Casticin, TNF-related apoptosis inducing ligand
Partner Name	Casticin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Phosphorylation	EIF2S1	hsa1965
	Up-regulation	Expression	ESR1	hsa2099
	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	BGC-823	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_3360
	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens (Human)	CVCL_5334
Result	Casticin enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-ER stress-CHOP pathway.

Pair Name	Capsaicin, TNF-related apoptosis inducing ligand
Partner Name	Capsaicin
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	POLD1	hsa5424
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	U-343MG	Glioblastoma	Homo sapiens (Human)	CVCL_S471
	T98G	Glioblastoma	Homo sapiens (Human)	CVCL_0556
	SNU-444	Glioblastoma	Homo sapiens (Human)	CVCL_5060
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	A combined regimen using capsaicin and TRAIL may provide a safe and effective strategy for treating malignant gliomas.

Pair Name	Cantharidin, TNF-related apoptosis inducing ligand
Partner Name	Cantharidin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Expression	SQSTM1	hsa8878
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
Result	The results of the present study revealed that cantharidin effectively sensitized cells to TRAIL‑mediated apoptosis and its effects are likely to be mediated by autophagy, the downregulation of c‑FLIP and the upregulation of DR‑5.

Pair Name	Butein, TNF-related apoptosis inducing ligand
Partner Name	Butein
Disease Info	[ICD-11: 2B33.4]	Leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	U-937	Adult acute monocytic leukemia	Homo sapiens (Human)	CVCL_0007
Result	Our data suggests that combined treatment with butein and TRAIL may provide a safe and effective strategy for treating cancer.

Pair Name	Bufalin, TNF-related apoptosis inducing ligand
Partner Name	Bufalin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	CBLB	hsa868
	Up-regulation	Expression	MAPK14	hsa1432
	Up-regulation	Expression	MAPK3	hsa5595
	Up-regulation	Expression	MAPK8	hsa5599
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
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
Result	Bufalin enhanced TRAIL-induced apoptosis by up-regulating the expression of DR4 and DR5. Bufalin-induced down-regulation of Cbl-b contributed to the up-regulation of DR4 and DR5, which might be partially mediated by the activation of ERK, JNK and p38 MAPK.

Pair Name	Beta-Elemene, TNF-related apoptosis inducing ligand
Partner Name	Beta-Elemene
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP8	hsa841
	Up-regulation	Expression	FADD	hsa8772
	Up-regulation	Expression	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	BGC-823	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_3360
	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
Result	Our results suggest that β-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

Pair Name	Bakuchiol, TNF-related apoptosis inducing ligand
Partner Name	Bakuchiol
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10A	hsa8797
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
Result	The collective results suggest that bakuchiol facilitates TRAIL-induced apoptosis in colon cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS/JNK pathway signals.

Pair Name	Artepillin C, TNF-related apoptosis inducing ligand
Partner Name	Artepillin C
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	NFKB1	hsa4790
	Up-regulation	Activity	RELA	hsa5970
In Vitro Model	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
Result	The data demonstrate the important role of Brazilian green propolis and its bioactive compounds in prostate cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	Sub-toxic dose of apigenin sensitizes HepG2 cells to TRAIL through ERK-dependent up-regulation of TRAIL receptor DR5

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2A90]	Anaplastic large cell lymphoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	CFLAR	hsa8837
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	Jurkat	Childhood T acute lymphoblastic leukemia	Homo sapiens (Human)	CVCL_0065
	SP+	Healthy	Homo sapiens (Human)	CVCL_1Y11
Result	Apigenin breaks TRAIL resistance in HTLV-1-associated ATL by transcriptional down-regulation of c-FLIP, a key inhibitor of death receptor signaling, and by up-regulation of TRAIL receptor 2 (TRAIL-R2)

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP6	hsa839
	Up-regulation	Cleavage	CASP7	hsa840
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0336
Result	Apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	CDH13	hsa1012
	Down-regulation	Expression	MAPK3	hsa5595
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
Result	Apigenin enhances TRAIL-induced antitumor activity in NSCLC cells by APG via inhibition of the NF-kappaB, AKT and ERK prosurvival regulators

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	BCL2	hsa596
	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
Result	Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Partner Name	Apigenin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
In Vitro Model	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
Result	Apigenin markedly augmented TRAIL-mediated apoptosis in prostate cancer cells

Pair Name	Angelicin, TNF-related apoptosis inducing ligand
Partner Name	Angelicin
Disease Info	[ICD-11: 2C90.Z]	Renal carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Down-regulation	Expression	CFLAR	hsa8837
In Vitro Model	Caki-1	Clear cell renal cell carcinoma	Homo sapiens (Human)	CVCL_0234
Result	This study provides evidence that angelicin might be a TRAIL sensitizer.

Pair Name	alpha-Mangostin, TNF-related apoptosis inducing ligand
Partner Name	alpha-Mangostin
Disease Info	[ICD-11: 2B66.0]	Oral squamous cell carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in the S/G2/M phase
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP7	hsa840
	Up-regulation	Activity	CASP9	hsa842
	Up-regulation	Expression	MYC	hsa4609
In Vitro Model	HSC-4	Tongue squamous cell carcinoma	Homo sapiens (Human)	CVCL_1289
	SAS	Tongue squamous cell carcinoma	Homo sapiens (Human)	CVCL_1675
Result	Synergism between α-mangostin and TRAIL induces apoptosis in squamous cell carcinoma of the oral cavity through the mitochondrial pathway

Pair Name	20(s)-ginsenoside Rh2, TNF-related apoptosis inducing ligand
Partner Name	20(s)-ginsenoside Rh2
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	CASP3	hsa836
	Down-regulation	Cleavage	CASP8	hsa841
	Down-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
	OV2944-LM-3	Malignant ovarian neoplasm	Mus musculus (Mouse)	CVCL_E956
	L-02	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_6926
In Vivo Model	Human hepatocellular carcinoma cells HepG2 (5×10⁵) in the log phase were implanted subcutaneously (s.c.) in the flanks of mice.
Result	Our study indicates that Rh2 may act as a sensitizer in combination with TRAIL to increase the efficacy of its anti-tumor activity.

Pair Name	Shogaol, TNF-related apoptosis inducing ligand
Partner Name	Shogaol
Disease Info	[ICD-11: 2B90]	Colon 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	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	Caco-2	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0025
	SW620	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0547
Result	This study gives rise to the possibility of applying shogaol as an antitumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant colon tumor therapy.

Pair Name	Curcumol, TNF-related apoptosis inducing ligand
Partner Name	Curcumol
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	NQO2	hsa4835
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1559
	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
In Vivo Model	BALB/c nude mice (5-week-old) were subcutaneously inoculated with A549 cells (1×10⁶)
Result	This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL-resistant cancers.

Pair Name	Morusin, TNF-related apoptosis inducing ligand
Partner Name	Morusin
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	EGFR	hsa1956
	Down-regulation	Phosphorylation	STAT3	hsa6774
	Up-regulation	Expression	TNFRSF10B	hsa8795
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
	LN-18	Glioblastoma	Homo sapiens (Human)	CVCL_0392
Result	These results suggest that morusin enhances TRAIL sensitivity in human glioblastoma cells through regulating expression of DR5 and EGFR. Therefore, the combination treatment of TRAIL and morusin may be a new therapeutic strategy for malignant glioma patients.