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

Scientific Reports
Farid Ahmad SiddiquiMohammad Askandar Iqbal

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.

References

Oct 20, 1995·The Journal of Biological Chemistry·S Singh, B B Aggarwal
Sep 21, 2002·Molecular and Cellular Biology·Christine C HudsonRobert T Abraham
May 15, 2004·Cancer Letters·G Radhakrishna PillaiEwa Carrier
Jul 22, 2004·British Journal of Cancer·P D HardtH U Kloer
Nov 2, 2004·Nature Reviews. Cancer·Robert A Gatenby, Robert J Gillies
May 16, 2007·The Journal of Biological Chemistry·Stephen C Land, Andrew R Tee
Jun 16, 2007·Advances in Experimental Medicine and Biology·Sulochana S Bhandarkar, Jack L Arbiser
Sep 13, 2008·Expert Review of Molecular Diagnostics·Philip D Hardt, Nils Ewald
Sep 17, 2008·Oncogene·T L Yuan, L C Cantley
Jan 30, 2009·Cancer Research·Christopher S BeeversShile Huang
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Mar 20, 2010·Nature Reviews. Cancer·Daniel A TennantEyal Gottlieb
Sep 22, 2010·Protein Science : a Publication of the Protein Society·Vibhor Gupta, Rameshwar N K Bamezai
Feb 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qian SunHongbing Zhang
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 6, 2012·Trends in Molecular Medicine·Liang Shen, Hong-Fang Ji
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 23, 2012·Genome Research·Suhaida A SelamatIte A Laird-Offringa
May 26, 2012·Trends in Biochemical Sciences·Barbara Chaneton, Eyal Gottlieb
Jan 1, 2013·Anti-cancer Agents in Medicinal Chemistry·Shile Huang
Apr 22, 2014·FEBS Letters·Mohd Askandar IqbalRameshwar N K Bamezai
Jan 7, 2016·Annals of Translational Medicine·Jiezhong ChenChen Chen
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale
Jul 8, 2016·Science Advances·Ralph J DeBerardinis, Navdeep S Chandel
Nov 9, 2016·Trends in Cancer·Arvindhan NagarajanNarendra Wajapeyee
Nov 23, 2016·Cancer Discovery·Claudio VernieriValter Longo
Jan 6, 2017·Cell Cycle·Adriana Borriello, Fulvio Della Ragione

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Citations

Feb 6, 2020·Biomolecules·Elizabeth VargheseDietrich Büsselberg
Feb 6, 2020·Cancers·Jessica RuzzoliniLido Calorini
Mar 4, 2020·International Journal of Molecular Sciences·Anamarija MojzešKoraljka Gall Trošelj
Mar 13, 2019·International Journal of Molecular Sciences·Renata Novak KujundžićKoraljka Gall Trošelj
Feb 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saleh A AlmatroodiArshad Husain Rahmani
Jul 4, 2020·Oxidative Medicine and Cellular Longevity·Ruiying TongLibing Ma
Apr 25, 2019·International Journal of Molecular Sciences·Ella WillenbacherAndreas Seeber
Sep 19, 2020·Cancer Cell International·Asad Ur RehmanSyed Akhtar Husain
Mar 2, 2019·International Journal of Molecular Sciences·Mhd Anas TomehXiubo Zhao
Aug 9, 2018·Frontiers in Cell and Developmental Biology·Elizabeth K Wiese, Taro Hitosugi
Nov 15, 2019·Journal of Cancer Research and Clinical Oncology·Devarajan NaliniGanesan Senthil Kumar
Feb 23, 2020·Seminars in Cancer Biology·Sajad FakhriAnupam Bishayee
Dec 20, 2020·Complementary Therapies in Clinical Practice·Elaheh ZareGholamreza Kavoosi
Oct 31, 2020·OncoTargets and Therapy·Guangjing HuangQian Fang
Nov 26, 2020·Drug Design, Development and Therapy·Ruo-Lan LiChun-Jie Wu
Apr 4, 2021·Biomolecules·Md Tanvir KabirMohamed M Abdel-Daim
May 29, 2021·Molecular Biology Reports·J R Dev ArundhathiChandra Prakash Prasad
Jun 9, 2021·Life Sciences·Abu Sufiyan Chhipa, Snehal Patel
Jun 17, 2021·Journal of Agricultural and Food Chemistry·Asifa KhanMohammad Askandar Iqbal
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana S DiasIola F Duarte
Oct 26, 2021·Frontiers in Oncology·Vivek Kumar SoniNaveen Kumar Vishvakarma
Nov 3, 2021·Journal of Medicinal Chemistry·Sahil AroraRaj Kumar
Sep 21, 2021·Anti-cancer Drugs·Caner KaracaGizem Calibasi-Kocal

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