Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition

Abstract Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose upt...

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Autores principales:	Farid Ahmad Siddiqui, Gopinath Prakasam, Shilpi Chattopadhyay, Asad Ur Rehman, Rayees Ahmad Padder, Mohammad Afaque Ansari, Rasha Irshad, Kailash Mangalhara, Rameshwar N. K. Bamezai, Mohammad Husain, Syed Mansoor Ali, Mohammad Askandar Iqbal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4e44a22eac149e0a5bfdd849c908dfc
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spelling	oai:doaj.org-article:a4e44a22eac149e0a5bfdd849c908dfc2021-12-02T15:08:40ZCurcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition10.1038/s41598-018-25524-32045-2322https://doaj.org/article/a4e44a22eac149e0a5bfdd849c908dfc2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25524-3https://doaj.org/toc/2045-2322Abstract Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis. Stable PKM2 silencing revealed that PKM2 is required for Warburg effect and proliferation of cancer cells. PKM2 over-expression abrogated the effects of curcumin, demonstrating that inhibition of Warburg effect by curcumin is PKM2-mediated. High PKM2 expression correlated strongly with poor overall survival in cancer, suggesting the requirement of PKM2 in cancer progression. The study unravels novel PKM2-mediated inhibitory effect of curcumin on metabolic capacities of cancer cells. To the best of our knowledge, this is the first study linking curcumin with PKM2-driven cancer glycolysis, thus, providing new perspectives into the mechanism of its anticancer activity.Farid Ahmad SiddiquiGopinath PrakasamShilpi ChattopadhyayAsad Ur RehmanRayees Ahmad PadderMohammad Afaque AnsariRasha IrshadKailash MangalharaRameshwar N. K. BamezaiMohammad HusainSyed Mansoor AliMohammad Askandar IqbalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Farid Ahmad Siddiqui Gopinath Prakasam Shilpi Chattopadhyay Asad Ur Rehman Rayees Ahmad Padder Mohammad Afaque Ansari Rasha Irshad Kailash Mangalhara Rameshwar N. K. Bamezai Mohammad Husain Syed Mansoor Ali Mohammad Askandar Iqbal Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
description	Abstract Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis. Stable PKM2 silencing revealed that PKM2 is required for Warburg effect and proliferation of cancer cells. PKM2 over-expression abrogated the effects of curcumin, demonstrating that inhibition of Warburg effect by curcumin is PKM2-mediated. High PKM2 expression correlated strongly with poor overall survival in cancer, suggesting the requirement of PKM2 in cancer progression. The study unravels novel PKM2-mediated inhibitory effect of curcumin on metabolic capacities of cancer cells. To the best of our knowledge, this is the first study linking curcumin with PKM2-driven cancer glycolysis, thus, providing new perspectives into the mechanism of its anticancer activity.
format	article
author	Farid Ahmad Siddiqui Gopinath Prakasam Shilpi Chattopadhyay Asad Ur Rehman Rayees Ahmad Padder Mohammad Afaque Ansari Rasha Irshad Kailash Mangalhara Rameshwar N. K. Bamezai Mohammad Husain Syed Mansoor Ali Mohammad Askandar Iqbal
author_facet	Farid Ahmad Siddiqui Gopinath Prakasam Shilpi Chattopadhyay Asad Ur Rehman Rayees Ahmad Padder Mohammad Afaque Ansari Rasha Irshad Kailash Mangalhara Rameshwar N. K. Bamezai Mohammad Husain Syed Mansoor Ali Mohammad Askandar Iqbal
author_sort	Farid Ahmad Siddiqui
title	Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
title_short	Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
title_full	Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
title_fullStr	Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
title_full_unstemmed	Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
title_sort	curcumin decreases warburg effect in cancer cells by down-regulating pyruvate kinase m2 via mtor-hif1α inhibition
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a4e44a22eac149e0a5bfdd849c908dfc
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Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition

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