ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway

Objective: Through comprehensive analysis of cisplatin-resistant HeLa cervical cancer cells, we reveal that curcumin exerts potent anti-cancer effects by modulating autophagic processes, and further identify Endoplasmic reticulum oxidoreductase 1-alpha (ERO1α) as a key regulator mediating this biolo...

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Main Authors: Dandan Huang, Bolorchimeg Baldandorj, Erdenezaya Odkhuu, Egshiglen Amartuvshin, Damdindorj Boldbaatar, Hairong Guo, Adilsaikhan Mendjargal
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cancer Treatment and Research Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468294225000930
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author Dandan Huang
Bolorchimeg Baldandorj
Erdenezaya Odkhuu
Egshiglen Amartuvshin
Damdindorj Boldbaatar
Hairong Guo
Adilsaikhan Mendjargal
author_facet Dandan Huang
Bolorchimeg Baldandorj
Erdenezaya Odkhuu
Egshiglen Amartuvshin
Damdindorj Boldbaatar
Hairong Guo
Adilsaikhan Mendjargal
author_sort Dandan Huang
collection DOAJ
description Objective: Through comprehensive analysis of cisplatin-resistant HeLa cervical cancer cells, we reveal that curcumin exerts potent anti-cancer effects by modulating autophagic processes, and further identify Endoplasmic reticulum oxidoreductase 1-alpha (ERO1α) as a key regulator mediating this biological response. Methods: Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8). The immunoblotting analysis measured the Phosphoinositide 3-Kinase/ Protein Kinase B (PI3K/AKT) pathway-related proteins, Microtubule-associated protein 1A/1B-light chain 3 (LC3II/I) ratio, and Beclin-1 expression. The cell migration ability was evaluated through a scratch assay. Results: Curcumin significantly inhibits the proliferation and migration of cisplatin-resistant HeLa cells. It promotes autophagy in these cells, as shown by the upregulation of autophagy-related proteins Beclin-1 and LC3II/I. Curcumin also downregulates ERO1α expression, subsequently modulating the PI3K/AKT pathway. Interestingly, the overexpression of ERO1α or activation of PI3K negated the autophagy-promoting effects of curcumin, indicated by the absence of changes in autophagy-related proteins and phosphorylation levels of PI3K/AKT. Conclusions: Our study provides compelling evidence that curcumin inhibits the proliferation and migration of cisplatin-resistant HeLa cells by promoting autophagy through the downregulation of ERO1α and inhibition of the PI3K/AKT pathway.
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spelling doaj-art-adb56af2ddb6409c9ab764a2e4aa98212025-08-20T03:27:44ZengElsevierCancer Treatment and Research Communications2468-29422025-01-014410095710.1016/j.ctarc.2025.100957ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathwayDandan Huang0Bolorchimeg Baldandorj1Erdenezaya Odkhuu2Egshiglen Amartuvshin3Damdindorj Boldbaatar4Hairong Guo5Adilsaikhan Mendjargal6Department of Obstetrics and Gynecology, School of Medicine, Mongolian National University of Medical Science, Mongolia; Department of Obstetrics and Gynecology, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia Autonomous Region, ChinaDepartment of Obstetrics and Gynecology, School of Medicine, Mongolian National University of Medical Science, MongoliaDepartment of Anatomy, School of Biomedicine, Institute of Biomedical Sciences, Mongolian National University of Medical Science, MongoliaDepartment of Anatomy, School of Biomedicine, Institute of Biomedical Sciences, Mongolian National University of Medical Science, MongoliaMongolian National University of Medical Science, MongoliaDepartment of Obstetrics and Gynecology, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia Autonomous Region, ChinaMongolia Japan Hospital, Mongolian National University of Medical Science, Mongolia; Correspondence author.Objective: Through comprehensive analysis of cisplatin-resistant HeLa cervical cancer cells, we reveal that curcumin exerts potent anti-cancer effects by modulating autophagic processes, and further identify Endoplasmic reticulum oxidoreductase 1-alpha (ERO1α) as a key regulator mediating this biological response. Methods: Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8). The immunoblotting analysis measured the Phosphoinositide 3-Kinase/ Protein Kinase B (PI3K/AKT) pathway-related proteins, Microtubule-associated protein 1A/1B-light chain 3 (LC3II/I) ratio, and Beclin-1 expression. The cell migration ability was evaluated through a scratch assay. Results: Curcumin significantly inhibits the proliferation and migration of cisplatin-resistant HeLa cells. It promotes autophagy in these cells, as shown by the upregulation of autophagy-related proteins Beclin-1 and LC3II/I. Curcumin also downregulates ERO1α expression, subsequently modulating the PI3K/AKT pathway. Interestingly, the overexpression of ERO1α or activation of PI3K negated the autophagy-promoting effects of curcumin, indicated by the absence of changes in autophagy-related proteins and phosphorylation levels of PI3K/AKT. Conclusions: Our study provides compelling evidence that curcumin inhibits the proliferation and migration of cisplatin-resistant HeLa cells by promoting autophagy through the downregulation of ERO1α and inhibition of the PI3K/AKT pathway.http://www.sciencedirect.com/science/article/pii/S2468294225000930CurcuminCervical cancerERO1αPI3K/AKT pathwayAutophagy
spellingShingle Dandan Huang
Bolorchimeg Baldandorj
Erdenezaya Odkhuu
Egshiglen Amartuvshin
Damdindorj Boldbaatar
Hairong Guo
Adilsaikhan Mendjargal
ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
Cancer Treatment and Research Communications
Curcumin
Cervical cancer
ERO1α
PI3K/AKT pathway
Autophagy
title ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
title_full ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
title_fullStr ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
title_full_unstemmed ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
title_short ERO1α regulates curcumin-induced autophagy via PI3K/AKT pathway
title_sort ero1α regulates curcumin induced autophagy via pi3k akt pathway
topic Curcumin
Cervical cancer
ERO1α
PI3K/AKT pathway
Autophagy
url http://www.sciencedirect.com/science/article/pii/S2468294225000930
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