ALA and Cancer
Most cancer cells utilize aerobic glycolysis, which is the preferential conversion of glucose to lactate for ATP generation, even when oxygen is present. This phenomenon, referred to as the Warburg effect, can be seen in cancer cells of different origin. Because aerobic glycolysis is grossly inefficient, producing only two molecules of ATP per molecule of glucose, cancer cells metabolize large amounts of glucose to keep up with their energy demands. Researchers hypothesized that by shifting cancer cell metabolism toward complete oxidation of glucose and away from aerobic glycolysis, they could effectively reduce proliferation of cancer cells.37
Because ALA is a cofactor of pyruvate dehydrogenase, it was a key consideration in nutrients that can steer energy production away from aerobic glycolysis and toward complete oxidation of glucose, resulting in a decrease in lactate production and an inhibition of glycolysis. Pre-clinical studies designed to investigate ALA’s role in this capacity demonstrated that ALA can reduce cancer cell viability and proliferation, as well as lactate production.37 ALA was also found to induce apoptosis in the following cell lines: neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3.
ALA also inhibits cancer cell proliferation and induces apoptosis by other mechanisms. The nutrient was found to inhibit cell proliferation and induce apoptosis in MDA-MB-231 breast cancer cell lines38 and to inhibit the colony-forming ability of the highly invasive MDA-MB-231 and 4T1 breast cancer cells. ALA inhibited the migration and invasion of metastatic breast cancer cells at least in part through inhibiting ERK1/2 and AKT signaling.39
Additionally, ALA has been shown to effectively induce apoptosis in human colon cancer cells (HT-29) by a pro-oxidant mechanism that is initiated by an increased uptake of oxidizable substrates into mitochondria,40 and ALA dramatically decreased non-small cell lung cancer (NSCLC) cell proliferation by down-regulating growth factor receptor-bound protein 2 (Grb2).41
Studies evaluating the efficacy of ALA in the inhibition/treatment of cancer are limited to experimental data; however, the research appears to be very promising.
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