l-Leucine induces growth arrest and persistent ERK activation in glioma cells

Most cancer cells undergo the Warburg effect, a shift from oxidative to glycolytic metabolism accompanied by suppression of p53. We have demonstrated leucine to stimulate mitochondrial biogenesis, fatty acid oxidation and p53 in both muscle and fat cells. Accordingly, we now sought to determine if leucine stimulates mitochondrial biogenesis and exit from the cell cycle in A‐375 melanoma cells 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 – 1.0 mM) dose‐responsively increased mitochondrial mass by 20–40% (p<0.001) under low glucose; its metabolite β‐hydroxy‐β‐methyl butyrate (50 μM) exerted similar effects, while amino acid controls valine and alanine exerted little effect (16–19% stimulation, p<0.05). In contrast, treatments were without significant effect under high glucose conditions. Despite the increase in mitochondrial mass at low glucose, treatments exerted no effect on cell proliferation, p53 or cyclin D. Thus, although both glucose reduction and increased leucine stimulate mitochondrial biogenesis, these effects are insufficient to stimulate p53, induce cell cycle arrest or reduce proliferation in these melanoma cells.

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l-Leucine induces growth arrest and persistent ERK activation in glioma cells

Cited by 2 publications

References 25 publications

Amino Acids in Cell Signaling: Regulation and Function

Amino Acids in Cell Signaling: Regulation and Function

Effects of leucine on mitochondrial biogenesis and cell cycle in A‐375 melanoma cells

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