InterPAD - DETAILS

MAPPPARVHLGAFLAVTPNPGSAASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMG
QHGPSARARAGRAPGPRPAREASPRLRVHKTFKFVVVGVLLQVVPSSAATIKLHDQSIGT
QQWEHSPLGELCPPGSHRSEHPGACNRCTEGVGYTNASNNLFACLPCTACKSDEEERSPC
TTTRNTACQCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIECVHKESGNGHNI
WVILVVTLVVPLLLVAVLIVCCCIGSGCGGDPKCMDRVCFWRLGLLRGPGAEDNAHNEIL
SNADSLSTFVSEQQMESQEPADLTGVTVQSPGEAQCLLGPAEAEGSQRRRLLVPANGADP
TETLMLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTG
RNASIHTLLDALERMEERHAREKIQDLLVDSGKFIYLEDGTGSAVSLE

No.	Title	Href
1	Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins. Biochem Biophys Res Commun. 2016 Apr 29;473(2):586-92. doi: 10.1016/j.bbrc.2016.03.127.	`Click`
2	Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89. doi: 10.1007/s00432-012-1204-4.	`Click`
3	Butein sensitizes human leukemia cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Arch Pharm Res. 2008 Sep;31(9):1179-86. doi: 10.1007/s12272-001-1286-2.	`Click`
4	EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line. J Huazhong Univ Sci Technolog Med Sci. 2009 Dec;29(6):771-5. doi: 10.1007/s11596-009-0620-4.	`Click`
5	Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5. Int J Oncol. 2012 Apr;40(4):1058-65. doi: 10.3892/ijo.2011.1299.	`Click`
6	Effects of A.marina-Derived Isoquercitrin on TNF-Related Apoptosis-Inducing Ligand Receptor (TRAIL-R) Expression and Apoptosis Induction in Cervical Cancer Cells. Appl Biochem Biotechnol. 2017 Jun;182(2):697-707. doi: 10.1007/s12010-016-2355-6.	`Click`
7	Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis. Mol Biol Rep. 2022 Jan;49(1):19-29. doi: 10.1007/s11033-021-06778-z.	`Click`
8	Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun. 2008 Oct 10;375(1):129-33. doi: 10.1016/j.bbrc.2008.07.131.	`Click`
9	Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells. Chem Biol Interact. 2022 Sep 25;365:110076. doi: 10.1016/j.cbi.2022.110076.	`Click`
10	Combining TRAIL and liquiritin exerts synergistic effects against human gastric cancer cells and xenograft in nude mice through potentiating apoptosis and ROS generation. Biomed Pharmacother. 2017 Sep;93:948-960. doi: 10.1016/j.biopha.2017.06.095.	`Click`
11	Morin enhances auranofin anticancer activity by up-regulation of DR4 and DR5 and modulation of Bcl-2 through reactive oxygen species generation in Hep3B human hepatocellular carcinoma cells. Phytother Res. 2019 May;33(5):1384-1393. doi: 10.1002/ptr.6329.	`Click`
12	Glioma progression is suppressed by Naringenin and APO2L combination therapy via the activation of apoptosis in vitro and in vivo. Invest New Drugs. 2020 Dec;38(6):1743-1754. doi: 10.1007/s10637-020-00979-2.	`Click`
13	Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway. Mol Carcinog. 2019 Jun;58(6):1033-1045. doi: 10.1002/mc.22991.	`Click`
14	Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy. J Exp Clin Cancer Res. 2019 Dec 21;38(1):501. doi: 10.1186/s13046-019-1498-z.	`Click`
15	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. J Agric Food Chem. 2017 Dec 27;65(51):11179-11191. doi: 10.1021/acs.jafc.7b02358.	`Click`
16	Tanshinone IIA sensitizes TRAIL-induced apoptosis in glioblastoma through inducing the expression of death receptors (and suppressing STAT3 activation). Brain Res. 2021 Sep 1;1766:147515. doi: 10.1016/j.brainres.2021.147515.	`Click`
17	Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis. Asian Pac J Cancer Prev. 2021 Sep 1;22(9):2855-2865. doi: 10.31557/APJCP.2021.22.9.2855.	`Click`

No.

Title

Href

Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins. Biochem Biophys Res Commun. 2016 Apr 29;473(2):586-92. doi: 10.1016/j.bbrc.2016.03.127.

Click

Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89. doi: 10.1007/s00432-012-1204-4.

Click

Butein sensitizes human leukemia cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Arch Pharm Res. 2008 Sep;31(9):1179-86. doi: 10.1007/s12272-001-1286-2.

Click

EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line. J Huazhong Univ Sci Technolog Med Sci. 2009 Dec;29(6):771-5. doi: 10.1007/s11596-009-0620-4.

Click

Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5. Int J Oncol. 2012 Apr;40(4):1058-65. doi: 10.3892/ijo.2011.1299.

Click

Effects of A.marina-Derived Isoquercitrin on TNF-Related Apoptosis-Inducing Ligand Receptor (TRAIL-R) Expression and Apoptosis Induction in Cervical Cancer Cells. Appl Biochem Biotechnol. 2017 Jun;182(2):697-707. doi: 10.1007/s12010-016-2355-6.

Click

Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis. Mol Biol Rep. 2022 Jan;49(1):19-29. doi: 10.1007/s11033-021-06778-z.

Click

Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun. 2008 Oct 10;375(1):129-33. doi: 10.1016/j.bbrc.2008.07.131.

Click

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells. Chem Biol Interact. 2022 Sep 25;365:110076. doi: 10.1016/j.cbi.2022.110076.

Click

Combining TRAIL and liquiritin exerts synergistic effects against human gastric cancer cells and xenograft in nude mice through potentiating apoptosis and ROS generation. Biomed Pharmacother. 2017 Sep;93:948-960. doi: 10.1016/j.biopha.2017.06.095.

Click

Morin enhances auranofin anticancer activity by up-regulation of DR4 and DR5 and modulation of Bcl-2 through reactive oxygen species generation in Hep3B human hepatocellular carcinoma cells. Phytother Res. 2019 May;33(5):1384-1393. doi: 10.1002/ptr.6329.

Click

Glioma progression is suppressed by Naringenin and APO2L combination therapy via the activation of apoptosis in vitro and in vivo. Invest New Drugs. 2020 Dec;38(6):1743-1754. doi: 10.1007/s10637-020-00979-2.

Click

Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway. Mol Carcinog. 2019 Jun;58(6):1033-1045. doi: 10.1002/mc.22991.

Click

Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy. J Exp Clin Cancer Res. 2019 Dec 21;38(1):501. doi: 10.1186/s13046-019-1498-z.

Click

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. J Agric Food Chem. 2017 Dec 27;65(51):11179-11191. doi: 10.1021/acs.jafc.7b02358.

Click

Tanshinone IIA sensitizes TRAIL-induced apoptosis in glioblastoma through inducing the expression of death receptors (and suppressing STAT3 activation). Brain Res. 2021 Sep 1;1766:147515. doi: 10.1016/j.brainres.2021.147515.

Click

Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis. Asian Pac J Cancer Prev. 2021 Sep 1;22(9):2855-2865. doi: 10.31557/APJCP.2021.22.9.2855.

Click

Name	Tumor necrosis factor receptor superfamily member 10A
UniProt ID	TR10A_HUMAN
Gene Name	TNFRSF10A
Gene ID	8797
Synonyms	TNFRSF10A, APO2, CD261, DR4, TRAILR-1, TRAILR1
Sequence	MAPPPARVHLGAFLAVTPNPGSAASGTEAAAATPSKVWGSSAGRIEPRGGGRGALPTSMG QHGPSARARAGRAPGPRPAREASPRLRVHKTFKFVVVGVLLQVVPSSAATIKLHDQSIGT QQWEHSPLGELCPPGSHRSEHPGACNRCTEGVGYTNASNNLFACLPCTACKSDEEERSPC TTTRNTACQCKPGTFRNDNSAEMCRKCSRGCPRGMVKVKDCTPWSDIECVHKESGNGHNI WVILVVTLVVPLLLVAVLIVCCCIGSGCGGDPKCMDRVCFWRLGLLRGPGAEDNAHNEIL SNADSLSTFVSEQQMESQEPADLTGVTVQSPGEAQCLLGPAEAEGSQRRRLLVPANGADP TETLMLFFDKFANIVPFDSWDQLMRQLDLTKNEIDVVRAGTAGPGDALYAMLMKWVNKTG RNASIHTLLDALERMEERHAREKIQDLLVDSGKFIYLEDGTGSAVSLE
Pathway Map	`MAP LINK`
KEGG ID	hsa8797
TTD ID	T77645
Pfam	PF00020; PF00531; PF20481

Pair Name	Bakuchiol, TNF-related apoptosis inducing ligand
Phytochemical	Bakuchiol
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Bufalin, TNF-related apoptosis inducing ligand
Phytochemical	Bufalin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Butein, TNF-related apoptosis inducing ligand
Phytochemical	Butein
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
Result	Our data suggests that combined treatment with butein and TRAIL may provide a safe and effective strategy for treating cancer.

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Phytochemical	Epigallocatechin gallate
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C30]	Melanoma	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
Result	EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line

Pair Name	Gomisin N, TNF-related apoptosis inducing ligand
Phytochemical	Gomisin N
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C77]	Cervical cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Isoquercitrin, TNF-related apoptosis inducing ligand
Phytochemical	Isoquercitrin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C77]	Cervical cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Kaempferol, TNF-related apoptosis inducing ligand
Phytochemical	Kaempferol
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2A20.1]	Chronic myelogenous leukemia	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Licochalcone B, TNF-related apoptosis inducing ligand
Phytochemical	Licochalcone B
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Liquiritin, TNF-related apoptosis inducing ligand
Phytochemical	Liquiritin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Morin, Auranofin
Phytochemical	Morin
Drug	Auranofin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
Result	This study provides evidence that morin can enhance the anticancer activity of AF in Hep3B human hepatocellular carcinoma cells, indicating that its combination could be an alternative treatment strategy for the hepatocellular carcinoma.

Pair Name	Naringenin, AMG-951
Phytochemical	Naringenin
Drug	AMG-951
Disease Info	[ICD-11: 2F7Z]	Glioma	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
Result	The present study provides a novel therapeutic strategy for glioma by potentiating APO2L-induced apoptosis via the combination with NG in glioma tumor cells.

Pair Name	Periplocin, TNF-related apoptosis inducing ligand
Phytochemical	Periplocin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
Result	Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway

Pair Name	Pterostilbene, TNF-related apoptosis inducing ligand
Phytochemical	Pterostilbene
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Tanshinone IIA, TNF-related apoptosis inducing ligand
Phytochemical	Tanshinone IIA
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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	Thymoquinone, TNF-related apoptosis inducing ligand
Phytochemical	Thymoquinone
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Up-regulation	Tumor necrosis factor receptor superfamily member 10A	Expression
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.