Tumor necrosis factor alpha induces Warburg‐like metabolism and is reversed by anti‐inflammatory curcumin in breast epithelial cells

The reprogramming of cellular metabolism in cancer cells is a well‐documented effect. It has previously been shown that common oncogene expression can induce aerobic glycolysis in cancer cells. However, the direct effect of an inflammatory microenvironment on cancer cell metabolism is not known. Here, we illustrate that treatment of nonmalignant (MCF‐10a) and malignant (MCF‐7) breast epithelial cells with low‐level (10 ng/ml) tumor necrosis factor alpha (TNF‐α) significantly increased glycolytic reliance, lactate export and expression of the glucose transporter 1 (GLUT1). TNF‐α decreased total mitochondrial content; however, oxygen consumption rate was not significantly altered, suggesting that overall mitochondrial function was increased. Upon glucose starvation, MCF7 cells treated with TNF‐α demonstrated significantly lower viability than nontreated cells. Interestingly, these properties can be partially reversed by coincubation with the anti‐inflammatory agent curcumin in a dose‐dependent manner. This work demonstrates that aerobic glycolysis can be directly induced by an inflammatory microenvironment independent of additional genetic mutations and signals from adjacent cells. Furthermore, we have identified that a natural dietary compound can reverse this effect. What's new? Oncogene expression can reprogram cell metabolism. In fact, most cancer cells have altered metabolism—specifically, increased aerobic glycolysis. Indirect evidence indicates that this type of altered metabolism may play an important role in tumorigenesis linked to inflammation. However, it wasn't known whether chronic inflammation can directly reprogram cell metabolism. In this study of normal and malignant breast epithelial cells, the authors found that the inflammatory cytokine TNF‐α can indeed directly induce metabolic changes, similar to those produced by oncogene expression. The study also found that this effect can be blocked by the natural dietary compound curcumin.