Quercetin exerts an inhibitory effect on cellular bioenergetics of the B164A5 murine melanoma cell line

Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured at 24, 48, and 72h of treatment of B164A5 murine melanoma cells with increasing concentrations (25, 50, 100, and 150 mu M) of quercetin using the extracellular flux analyzer Seahorse XF24e (Seahorse Agilent). Analysis of mitochondrial function was performed in the presence of the classic modulators of the electron transport chain: oligomycin, FCCP, and rotenone. 72-h treatment with quercetin induced a dose-dependent decrease of all OCR parameters (basal respiration, proton leak, ATP turnover, maximal respiration, reserve capacity) as well as of ECAR. At variance, 48-h treatment induced a decrease of OCR and ECAR when quercetin was applied at 50, 100, and 150 mu M, while the 24-h treatment induced a decrease of bioenergetic parameters only for the highest concentrations (100 and 150 mu M) of the compound. Our data clearly demonstrated that quercetin elicited dose-dependent inhibitory effect on examined parameters of cellular bioenergetics that was most potent at 72h of treatment. Thereby quercetin, modulating both glycolytic and mitochondrial pathways for ATP production, might be an efficient approach in killing cancer cells.