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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25524-3 |
| _version_ | 1818996028565618688 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T21:23:14Z |
| format | Article |
| id | doaj.art-a4e44a22eac149e0a5bfdd849c908dfc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:23:14Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a4e44a22eac149e0a5bfdd849c908dfc2022-12-21T19:26:13ZengNature PortfolioScientific Reports2045-23222018-05-01811910.1038/s41598-018-25524-3Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibitionFarid Ahmad Siddiqui0Gopinath Prakasam1Shilpi Chattopadhyay2Asad Ur Rehman3Rayees Ahmad Padder4Mohammad Afaque Ansari5Rasha Irshad6Kailash Mangalhara7Rameshwar N. K. Bamezai8Mohammad Husain9Syed Mansoor Ali10Mohammad Askandar Iqbal11Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarSchool of Life Sciences, Jawaharlal Nehru University, New Mehrauli RoadDepartment of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard (Deemed University)Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarSchool of Life Sciences, Jawaharlal Nehru University, New Mehrauli RoadSchool of Life Sciences, Jawaharlal Nehru University, New Mehrauli RoadDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarDepartment of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia NagarAbstract 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.https://doi.org/10.1038/s41598-018-25524-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-018-25524-3 |
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