title: Tumor necrosis factor alpha induces Warburg-like metabolism and is reversed by anti-inflammatory curcumin in breast epithelial cells.
abstract: 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.
authors: Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM; Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM; Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM.
authors: Roger A
authors: RA
authors: Vaughan
authors: Randi
authors: R
authors: Garcia-Smith
authors: Jonathan
authors: J
authors: Dorsey
authors: Jeffrey K
authors: JK
authors: Griffith
authors: Marco
authors: M
authors: Bisoffi
authors: Kristina A
authors: KA
authors: Trujillo
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001940:Breast / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D061986:MCF-7 Cells; D008928:Mitochondria / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D058494:Walker-Warburg Syndrome / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; C495677:SLC2A1 protein, human; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D003474:Curcumin; D005947:Glucose
keywords: aerobic glycolysis; breast cancer; inflammation; mitochondria; oxidative phosphorylation