InterPAD - DETAILS

MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAAFGLGAAAAPTSATRVP
AAGAVAAAEVTVEDAEALPAAAGEQEPRGPEPDDETELRPRGRSLVIISTLDGRIAALDP
ENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGALFQWDQDRESMETVPFTVES
LLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSALGCRQWDSDEMEQEEDILLLQR
TQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRAGFIESTFKPNENTEESKIISDVEE
QEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQFCTPIASAWLLKDGKVIPISLFDDTS
YTSNDDVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRISEKFPSSPKALESVTNE
NAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKFSHEEYSNGALSILQYPYDNGY
YLPYYKRERNKRSTQITVRFLDNPHYNKNIRKKDPVLLLHWWKEIVATILFCIIATTFIV
RRLFHPHPHRQRKESETQCQTENKYDSVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLG
RGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLE
APPEKWQEKMDEIWLKDESTDWPLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSR
SFSVGISCDQTSSSESQFSPLEFSGMDHEDISESVDAAYNLQDSCLTDCDVEDGTMDGND
EGHSFELCPSEASPYVRSRERTSSSIVFEDSGCDNASSKEEPKTNRLHIGNHCANKLTAF
KPTSSKSSSEATLSISPPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWM
NGRCTIEERERSVCLHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVT
AMDQDEEEQTVLTPMPAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYP
FSTQMERVRTLTDVRNLKFPPLFTQKYPCEYVMVQDMLSPSPMERPEAINIIENAVFEDL
DFPGKTVLRQRSRSLSSSGTKHSRQSNNSHSPLPSN

No.	Title	Href
1	Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers. Br J Pharmacol. 2016 Mar;173(6):1033-44. doi: 10.1111/bph.13408.	`Click`
2	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`
3	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`
4	Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non-small cell lung cancer cells via endoplasmic reticulum stress-mediated degradation of Mcl-1. Mol Carcinog. 2020 Jun;59(6):590-603. doi: 10.1002/mc.23184.	`Click`
5	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`
6	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`
7	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`
8	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`
9	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`
10	Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib. ACS Chem Neurosci. 2020 May 6;11(9):1337-1346. doi: 10.1021/acschemneuro.0c00095.	`Click`
11	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`
12	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`

No.

Title

Href

Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers. Br J Pharmacol. 2016 Mar;173(6):1033-44. doi: 10.1111/bph.13408.

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

Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non-small cell lung cancer cells via endoplasmic reticulum stress-mediated degradation of Mcl-1. Mol Carcinog. 2020 Jun;59(6):590-603. doi: 10.1002/mc.23184.

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

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

Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib. ACS Chem Neurosci. 2020 May 6;11(9):1337-1346. doi: 10.1021/acschemneuro.0c00095.

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

Name	Eukaryotic translation initiation factor 2-alpha kinase 3
UniProt ID	E2AK3_HUMAN
Gene Name	EIF2AK3
Gene ID	9451
Synonyms	EIF2AK3, PEK, PERK, WRS
Sequence	MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAAFGLGAAAAPTSATRVP AAGAVAAAEVTVEDAEALPAAAGEQEPRGPEPDDETELRPRGRSLVIISTLDGRIAALDP ENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGALFQWDQDRESMETVPFTVES LLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSALGCRQWDSDEMEQEEDILLLQR TQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRAGFIESTFKPNENTEESKIISDVEE QEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQFCTPIASAWLLKDGKVIPISLFDDTS YTSNDDVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRISEKFPSSPKALESVTNE NAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKFSHEEYSNGALSILQYPYDNGY YLPYYKRERNKRSTQITVRFLDNPHYNKNIRKKDPVLLLHWWKEIVATILFCIIATTFIV RRLFHPHPHRQRKESETQCQTENKYDSVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLG RGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLE APPEKWQEKMDEIWLKDESTDWPLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSR SFSVGISCDQTSSSESQFSPLEFSGMDHEDISESVDAAYNLQDSCLTDCDVEDGTMDGND EGHSFELCPSEASPYVRSRERTSSSIVFEDSGCDNASSKEEPKTNRLHIGNHCANKLTAF KPTSSKSSSEATLSISPPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWM NGRCTIEERERSVCLHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVT AMDQDEEEQTVLTPMPAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYP FSTQMERVRTLTDVRNLKFPPLFTQKYPCEYVMVQDMLSPSPMERPEAINIIENAVFEDL DFPGKTVLRQRSRSLSSSGTKHSRQSNNSHSPLPSN
Pathway Map	`MAP LINK`
T.C. Number	8.A.23.1.57
KEGG ID	hsa9451
TTD ID	T13176
Pfam	PF00069; PF03109; PF03137; PF06293; PF07714; PF14531

Pair Name	Decursin, TNF-related apoptosis inducing ligand
Phytochemical	Decursin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	Activity
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	Kaempferol, Cisplatin
Phytochemical	Kaempferol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	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	Down-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	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	Phenethyl isothiocyanate, Gefitinib
Phytochemical	Phenethyl isothiocyanate
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	Phosphorylation
Result	We explored the prospect of PEITC in improving the efficacy of targeted drug therapy and demonstrated the synergistic effects and underlined mechanisms of PEITC combined with Gefitinib in NSCLC cells treatment. This study provided useful information for developing novel therapy strategies by combination treatment of PEITC with targeted drugs.

Pair Name	Phenethyl isothiocyanate, Irinotecan
Phytochemical	Phenethyl isothiocyanate
Drug	Irinotecan
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	Phosphorylation
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	Pristimerin, Sorafenib
Phytochemical	Pristimerin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	Phosphorylation
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	Eukaryotic translation initiation factor 2-alpha kinase 3	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	Eukaryotic translation initiation factor 2-alpha kinase 3	Phosphorylation
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	Eukaryotic translation initiation factor 2-alpha kinase 3	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	Ursodiol, Bortezomib
Phytochemical	Ursodiol
Drug	Bortezomib
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	Expression
Result	Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib

Pair Name	Withaferin A, Fluorouracil
Phytochemical	Withaferin A
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Eukaryotic translation initiation factor 2-alpha kinase 3	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	Eukaryotic translation initiation factor 2-alpha kinase 3	Phosphorylation
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.