Inverse correlation between heme synthesis and the Warburg effect in cancer cells

AbstractsCancer cells show a bias toward the glycolytic system over the conventional mitochondrial electron transfer system for obtaining energy. This biased metabolic adaptation is called the Warburg effect. Cancer cells also exhibit a characteristic metabolism, a decreased heme synthesizing ability. Here we show that heme synthesis and the Warburg effect are inversely correlated. We used human gastric cancer cell lines to investigate glycolytic metabolism and electron transfer system toward promotion/inhibition of heme synthesis. Under hypoxic conditions, heme synthesis was suppressed and the glycolytic system was enhanced. Addition of a heme precursor for the promotion of heme synthesis led to an enhanced electron transfer system and inhibited the glycolytic system and vice versa. Enhanced heme synthesis leads to suppression of cancer cell proliferation by increasing intracellular reactive oxygen species levels. Collectively, the promotion of heme synthesis in cancer cells eliminated the Warburg effect by shifting energy metabolism from glycolysis to oxidative phosphorylation.