InterPAD - DETAILS

MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNR
ITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVV
EKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQ
RQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNG
VFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS
SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIV
LVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVC
PLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLG
TFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIER
MVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE
KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL

No.	Title	Href
1	Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response. Mol Med Rep. 2016 Sep;14(3):2679-84. doi: 10.3892/mmr.2016.5533.	`Click`
2	Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. PLoS One. 2013;8(3):e58855. doi: 10.1371/journal.pone.0058855.	`Click`
3	Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78. Sci Rep. 2023 Dec 19;13(1):22661. doi: 10.1038/s41598-023-49604-1.	`Click`
4	Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer. Cancer Biol Ther. 2016 Oct 2;17(10):1022-1029. doi: 10.1080/15384047.2016.1219810.	`Click`
5	(-)-Epigallocatechin Gallate (EGCG) Enhances the Sensitivity of Colorectal Cancer Cells to 5-FU by Inhibiting GRP78/NF-κB/miR-155-5p/MDR1 Pathway. J Agric Food Chem. 2019 Mar 6;67(9):2510-2518. doi: 10.1021/acs.jafc.8b06665.	`Click`
6	Kaempferol Induces Cell Death in A2780 Ovarian Cancer Cells and Increases Their Sensitivity to Cisplatin by Activation of Cytotoxic Endoplasmic Reticulum-Mediated Autophagy and Inhibition of Protein Kinase B. Folia Biol (Praha). 2020;66(1):36-46.	`Click`
7	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`
8	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. Cell Death Dis. 2014 Oct 16;5(10):e1465. doi: 10.1038/cddis.2014.429.	`Click`
9	Phenethyl isothiocyanate and irinotecan synergistically induce cell apoptosis in colon cancer HCT 116 cells in vitro. Environ Toxicol. 2024 Jan;39(1):457-469. doi: 10.1002/tox.23993.	`Click`
10	Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells. Cell Death Discov. 2023 Oct 13;9(1):375. doi: 10.1038/s41420-023-01672-y.	`Click`
11	Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27kip1 signaling pathway. Phytomedicine. 2021 Jun;86:153563. doi: 10.1016/j.phymed.2021.153563.	`Click`
12	Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest. Oncol Rep. 2020 Oct;44(4):1605-1615. doi: 10.3892/or.2020.7708.	`Click`
13	6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells. Int J Mol Sci. 2023 Jan 30;24(3):2639. doi: 10.3390/ijms24032639.	`Click`
14	Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway. Eur J Med Res. 2023 Oct 27;28(1):462. doi: 10.1186/s40001-023-01420-z.	`Click`
15	Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells. Am J Cancer Res. 2020 Mar 1;10(3):799-815.	`Click`
16	Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J Biol Chem. 2014 Aug 1;289(31):21544-61. doi: 10.1074/jbc.M114.558890.	`Click`
17	Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction. Cell Oncol (Dordr). 2021 Feb;44(1):135-150. doi: 10.1007/s13402-020-00557-x.	`Click`

No.

Title

Href

Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response. Mol Med Rep. 2016 Sep;14(3):2679-84. doi: 10.3892/mmr.2016.5533.

Click

Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. PLoS One. 2013;8(3):e58855. doi: 10.1371/journal.pone.0058855.

Click

Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78. Sci Rep. 2023 Dec 19;13(1):22661. doi: 10.1038/s41598-023-49604-1.

Click

Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer. Cancer Biol Ther. 2016 Oct 2;17(10):1022-1029. doi: 10.1080/15384047.2016.1219810.

Click

(-)-Epigallocatechin Gallate (EGCG) Enhances the Sensitivity of Colorectal Cancer Cells to 5-FU by Inhibiting GRP78/NF-κB/miR-155-5p/MDR1 Pathway. J Agric Food Chem. 2019 Mar 6;67(9):2510-2518. doi: 10.1021/acs.jafc.8b06665.

Click

Kaempferol Induces Cell Death in A2780 Ovarian Cancer Cells and Increases Their Sensitivity to Cisplatin by Activation of Cytotoxic Endoplasmic Reticulum-Mediated Autophagy and Inhibition of Protein Kinase B. Folia Biol (Praha). 2020;66(1):36-46.

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

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. Cell Death Dis. 2014 Oct 16;5(10):e1465. doi: 10.1038/cddis.2014.429.

Click

Phenethyl isothiocyanate and irinotecan synergistically induce cell apoptosis in colon cancer HCT 116 cells in vitro. Environ Toxicol. 2024 Jan;39(1):457-469. doi: 10.1002/tox.23993.

Click

Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells. Cell Death Discov. 2023 Oct 13;9(1):375. doi: 10.1038/s41420-023-01672-y.

Click

Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27kip1 signaling pathway. Phytomedicine. 2021 Jun;86:153563. doi: 10.1016/j.phymed.2021.153563.

Click

Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest. Oncol Rep. 2020 Oct;44(4):1605-1615. doi: 10.3892/or.2020.7708.

Click

6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells. Int J Mol Sci. 2023 Jan 30;24(3):2639. doi: 10.3390/ijms24032639.

Click

Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway. Eur J Med Res. 2023 Oct 27;28(1):462. doi: 10.1186/s40001-023-01420-z.

Click

Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells. Am J Cancer Res. 2020 Mar 1;10(3):799-815.

Click

Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J Biol Chem. 2014 Aug 1;289(31):21544-61. doi: 10.1074/jbc.M114.558890.

Click

Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction. Cell Oncol (Dordr). 2021 Feb;44(1):135-150. doi: 10.1007/s13402-020-00557-x.

Click

Name	Endoplasmic reticulum chaperone BiP
UniProt ID	BIP_HUMAN
Gene Name	HSPA5
Gene ID	3309
Synonyms	HSPA5, BIP, GRP78, HEL-S-89n
Sequence	MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNR ITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVV EKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQ RQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNG VFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIV LVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVC PLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLG TFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIER MVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL
Pathway Map	`MAP LINK`
T.C. Number	1.A.33.1.5
KEGG ID	hsa3309
TTD ID	T77594
Pfam	PF00012; PF01968; PF02782; PF05318; PF06723; PF08841; PF14450; PF21523

Pair Name	Anacardic Acid, Bortezomib
Phytochemical	Anacardic Acid
Drug	Bortezomib
Disease Info	[ICD-11: 2A83]	Multiple myeloma	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment.

Pair Name	Casticin, TNF-related apoptosis inducing ligand
Phytochemical	Casticin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
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	Corilagin, Fluorouracil
Phytochemical	Corilagin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.

Pair Name	Curcumin, Fenretinide
Phytochemical	Curcumin
Drug	Fenretinide
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Our findings suggest that the 2 small molecules, when used in combination, can potentially be effective therapeutic agents for treating NSCLC, at least in part, by regulating endoplasmic reticulum (ER) chaperone protein GRP78.

Pair Name	Epigallocatechin gallate, Fluorouracil
Phytochemical	Epigallocatechin gallate
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Our data show that EGCG may be act as a novel chemo-sensitizer, and the GRP78/NF-κB/miR-155-5p/MDR1 pathway plays a vital role in EGCG enhancing the sensitivity of colorectal cancer to 5-FU.

Pair Name	Kaempferol, Cisplatin
Phytochemical	Kaempferol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Kaempferol Induces cell death in A2780 ovarian cancer cells and increases their sensitivity to cisplatin by activation of cytotoxic endoplasmic reticulum-mediated autophagy and inhibition of protein kinase B

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	Endoplasmic reticulum chaperone BiP	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	Medicarpin, TNF-related apoptosis inducing ligand
Phytochemical	Medicarpin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B33.1]	Myeloid leukemia	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
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	Phenethyl isothiocyanate, Irinotecan
Phytochemical	Phenethyl isothiocyanate
Drug	Irinotecan
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	PEITC potentiates IRI anticancer activity by promoting cell apoptosis in the human colon HCT 116 cells. Thus, PEITC may be a potential enhancer for IRI in humans as an anticolon cancer drug in the future.

Pair Name	Piperlongumine, HSP90 inhibitors
Phytochemical	Piperlongumine
Drug	HSP90 inhibitors
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells

Pair Name	Pristimerin, Sorafenib
Phytochemical	Pristimerin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27kip1 signaling pathway

Pair Name	Resveratrol, Cisplatin
Phytochemical	Resveratrol
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	These results indicated that RES is a promising adjuvant for DDP during GC chemotherapy.

Pair Name	Shogaol, Gefitinib
Phytochemical	Shogaol
Drug	Gefitinib
Disease Info	[ICD-11: 2C73]	Ovarian Cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer.

Pair Name	Tannic acid, Cisplatin
Phytochemical	Tannic acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.

Pair Name	Withaferin A, Fluorouracil
Phytochemical	Withaferin A
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells

Pair Name	Zerumbone, Celecoxib
Phytochemical	Zerumbone
Drug	Celecoxib
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy.

Pair Name	Honokiol, Paclitaxel
Phytochemical	Honokiol
Drug	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Endoplasmic reticulum chaperone BiP	Expression
Result	Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction