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.
Highlights
Metabolic priorities of cancer cells differ remarkably from normal cells, providing a new therapeutic window
The effect of curcumin on Warburg effect was studied by measuring the rate of glucose uptake and lactate production in cancer cell lines- lung (H1299), breast (MCF-7), cervical (HeLa) and prostate (PC3) and human embryonic kidney (HEK) 293 cells, taken as control
Significant inhibition in glucose uptake and lactate release was observed across the four cell lines, no appreciable decrease in Warburg effect was observed in HEK 293 cells (Fig. 1a,b)
Summary
Metabolic priorities of cancer cells differ remarkably from normal cells, providing a new therapeutic window. Warburg effect is characterized by high glucose uptake and lactate release and is considered as a hallmark of most tumors[3]. This metabolic adaptation benefits cancer cells in surviving through hypoxic conditions, commonly found in tumors, and to support their anabolic requirements[4,5]. Extensive studies have shown that pyruvate kinase M2 (PKM2) is one of the critical regulator of Warburg effect[12,13]. Numerous studies have shown the anti-cancer properties of curcumin in a wide variety of cell lines and animals[27,28,29,30,31,32,33]. Our results identify a new anti-cancer mechanism of curcumin and endorse its therapeutic relevance in inhibiting cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
