The Effects of Leucine on Mitochondrial Biogenesis and Cell Cycle in A-375 Melanoma Cells

Most cancer cells undergo the Warburg effect, a shift from oxidative to glycolytic metabolism accompanied by suppression of p53. We have demonstrated leucine stimulation of mitochondrial biogenesis, fatty acid oxidation, and p53 expression in both muscle and fat cells. Accordingly, we now sought to determine if leucine stimulates mitochondrial biogenesis and exit from cell cycle in A-375 melanoma cells. Because these cells use glucose as their primary substrate, cells were grown under both standard (11.1 mM) and reduced (5.5 mM) glucose conditions. Increasing glucose reduced mitochondrial mass 50-60%, and accelerated cell proliferation by ~20%. Leucine (0.25, 0.5, 0.75, and 1.0 mM) dose-responsively increased mitochondrial mass 20-40% (p