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Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Biochem+Biophys 2016 ; 74 (3): 427-34 Nephropedia Template TP
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Oleanolic acid inhibits high salt induced exaggeration of Warburg-like metabolism in breast cancer cells #MMPMID27236294
Amara S; Zheng M; Tiriveedhi V
Cell Biochem Biophys 2016[Sep]; 74 (3): 427-34 PMID27236294show ga
Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg-effect) for their macromolecule synthesis. Although the exact causes of this Warburg-effect are unclear, high osmotic stress in solid tumor microenvironment is considered as one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt mediated osmotic stress induced cancer growth. Hypertonic (0.16M NaCl) culture conditions enhanced the cancer cell growth (26%, p<0.05) and aerobic glycolysis as marked by increased glucose consumption (34%, p<0.05) and lactate production (25%, p<0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely, hexokinase, pyruvate kinase-typeM2 and lactate dehydrogenase-A. Interestingly, this high salt mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt mediated inhibition of cytochrome oxidase, caspase activity and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt mediated osmotic stress along with potential application of OA in anti-cancer therapy.