InterPAD - DETAILS

MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYR
GFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFA
AGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRY
GPMEEPLVIEKDLPHYF

No.	Title	Href
1	Artesunate synergistically promotes sorafenib‑induced apoptosis and ferroptosis in non‑Hodgkin lymphoma cells through inhibition of the STAT3 pathway. Oncol Rep. 2023 Jul;50(1):147. doi: 10.3892/or.2023.8584.	`Click`
2	Baicalin enhances the efficacy of 5-Fluorouracil in gastric cancer by promoting ROS-mediated ferroptosis. Biomed Pharmacother. 2023 Aug;164:114986. doi: 10.1016/j.biopha.2023.114986.	`Click`
3	Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics. 2020;10(11):5107-5119. Published 2020 Apr 6. doi:10.7150/thno.44705	`Click`
4	Dihydroartemisinin enhances the inhibitory effect of sorafenib on HepG2 cells by inducing ferroptosis and inhibiting energy metabolism. J Pharmacol Sci. 2022 Jan;148(1):73-85. doi: 10.1016/j.jphs.2021.09.008.	`Click`
5	Role of Escin in breast cancer therapy: potential mechanism for inducing ferroptosis and synergistic antitumor activity with cisplatin. Apoptosis. 2023 Aug;28(7-8):1154-1167. doi: 10.1007/s10495-023-01849-x.	`Click`
6	Luteolin exhibits synergistic therapeutic efficacy with erastin to induce ferroptosis in colon cancer cells through the HIC1-mediated inhibition of GPX4 expression. Free Radic Biol Med. 2023 Nov 1;208:530-544. doi: 10.1016/j.freeradbiomed.2023.09.014.	`Click`
7	Tiliroside targets TBK1 to induce ferroptosis and sensitize hepatocellular carcinoma to sorafenib. Phytomedicine. 2023 Mar;111:154668. doi: 10.1016/j.phymed.2023.154668.	`Click`
8	Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin. Mol Med Rep. 2023 Jan;27(1):17. doi: 10.3892/mmr.2022.12904.	`Click`
9	Zerumbone combined with gefitinib alleviates lung cancer cell growth through the AKT/STAT3/SLC7A11 axis. Neoplasma. 2023 Feb;70(1):58-70. doi: 10.4149/neo_2022_220418N423.	`Click`
10	Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.	`Click`
11	Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. Phytomedicine. 2023 Apr;112:154701. doi: 10.1016/j.phymed.2023.154701.	`Click`

No.

Title

Href

Artesunate synergistically promotes sorafenib‑induced apoptosis and ferroptosis in non‑Hodgkin lymphoma cells through inhibition of the STAT3 pathway. Oncol Rep. 2023 Jul;50(1):147. doi: 10.3892/or.2023.8584.

Click

Baicalin enhances the efficacy of 5-Fluorouracil in gastric cancer by promoting ROS-mediated ferroptosis. Biomed Pharmacother. 2023 Aug;164:114986. doi: 10.1016/j.biopha.2023.114986.

Click

Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics. 2020;10(11):5107-5119. Published 2020 Apr 6. doi:10.7150/thno.44705

Click

Dihydroartemisinin enhances the inhibitory effect of sorafenib on HepG2 cells by inducing ferroptosis and inhibiting energy metabolism. J Pharmacol Sci. 2022 Jan;148(1):73-85. doi: 10.1016/j.jphs.2021.09.008.

Click

Role of Escin in breast cancer therapy: potential mechanism for inducing ferroptosis and synergistic antitumor activity with cisplatin. Apoptosis. 2023 Aug;28(7-8):1154-1167. doi: 10.1007/s10495-023-01849-x.

Click

Luteolin exhibits synergistic therapeutic efficacy with erastin to induce ferroptosis in colon cancer cells through the HIC1-mediated inhibition of GPX4 expression. Free Radic Biol Med. 2023 Nov 1;208:530-544. doi: 10.1016/j.freeradbiomed.2023.09.014.

Click

Tiliroside targets TBK1 to induce ferroptosis and sensitize hepatocellular carcinoma to sorafenib. Phytomedicine. 2023 Mar;111:154668. doi: 10.1016/j.phymed.2023.154668.

Click

Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin. Mol Med Rep. 2023 Jan;27(1):17. doi: 10.3892/mmr.2022.12904.

Click

Zerumbone combined with gefitinib alleviates lung cancer cell growth through the AKT/STAT3/SLC7A11 axis. Neoplasma. 2023 Feb;70(1):58-70. doi: 10.4149/neo_2022_220418N423.

Click

Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.

Click

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

Click

Name	Phospholipid hydroperoxide glutathione peroxidase GPX4
UniProt ID	GPX4_HUMAN
Gene Name	GPX4
Gene ID	2879
Synonyms	GPX4, GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx, snPHGPx
Sequence	MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYR GFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFA AGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRY GPMEEPLVIEKDLPHYF
Pathway Map	`MAP LINK`
KEGG ID	hsa2879
Pfam	PF00255; PF00578

Pair Name	Artesunate, Sorafenib
Phytochemical	Artesunate
Drug	Sorafenib
Disease Info	[ICD-11: XH50P3]	Non‑hodgkin lymphoma	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Artesunate synergistically promotes sorafenib‑induced apoptosis and ferroptosis in non‑Hodgkin lymphoma cells through inhibition of the STAT3 pathway

Pair Name	Baicalin, Fluorouracil
Phytochemical	Baicalin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Baicalin inhibits GC and enhances 5-Fu by promoting ROS-related ferroptosis in GC.

Pair Name	Beta-Elemene, Cetuximab
Phytochemical	Beta-Elemene
Drug	Cetuximab
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	natural product β-elemene is a new ferroptosis inducer and combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant CRC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for CRC patients with RAS mutations.

Pair Name	Dihydroartemisinin, Sorafenib
Phytochemical	Dihydroartemisinin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	DHA and Sora had the same mechanism, and the combined application of them could have a synergistic anti-tumor effect by inducing ferroptosis and inhibiting energy metabolism in HepG2 cells.

Pair Name	Escin, Cisplatin
Phytochemical	Escin
Drug	Cisplatin
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Role of Escin in breast cancer therapy: potential mechanism for inducing ferroptosis and synergistic antitumor activity with cisplatin

Pair Name	Luteolin, Erastin
Phytochemical	Luteolin
Drug	Erastin
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	These results clearly demonstrated that luteolin acts synergistically with erastin and renders colon cancer cells vulnerable to ferroptosis through the HIC1-mediated inhibition of GPX4 expression, which may act as a promising therapeutic strategy.

Pair Name	Tiliroside, Sorafenib
Phytochemical	Tiliroside
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Our findings imply that tiliroside is a potent TBK1 inhibitor and a candidate natural anti-cancer product that could function as a sensitizer of sorafenib in HCC treatment by targeting TBK1 to induce ferroptosis.

Pair Name	Triptolide, Doxorubicin
Phytochemical	Triptolide
Drug	Doxorubicin
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	The present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolide‑induced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.

Pair Name	Zerumbone, Gefitinib
Phytochemical	Zerumbone
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Our study suggested that zerumbone combined with gefitinib could effectively inhibit lung cancer for multi-model therapies, including the inhibition of tumor growth, angiogenesis, induce cell apoptosis, and ferroptosis.

Pair Name	2,3,5,6-Tetramethylpyrazine, Cisplatin
Phytochemical	2,3,5,6-Tetramethylpyrazine
Drug	Cisplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	A series of ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and evaluated for their anti-proliferative potency and generated an optimal platinum(IV) complex 16a. The above-described results indicated that 16a obtained different anti-cancer mechanisms of CDDP, which could initiate mitochondria-dependent apoptosis and xCT-GPX4 axial-mediated ferroptosis in PANC-1/CDDP cells.

Pair Name	Shikonin, Cisplatin
Phytochemical	Shikonin
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer	Investigative
Regulate Info	Down-regulation	Phospholipid hydroperoxide glutathione peroxidase GPX4	Expression
Result	Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation