Melatonin reverses warburg effect
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Melatonin acts as a potent anti-Warburg agent in cancer cells by inhibiting aerobic glycolysis, reducing lactate production, and reversing the metabolic shift towards oxidative phosphorylation (OXPHOS). It suppresses tumor growth by re-routing pyruvate into the mitochondria, inhibiting key enzymes like pyruvate dehydrogenase kinase (PDK), and promoting apoptosis in various cancer cell lines.
Key Aspects of Melatonin's Impact on the Warburg Effect:
Inhibition of Aerobic Glycolysis: Melatonin reduces the rapid consumption of glucose and lactate production (the hallmarks of the Warburg effect) in cancer cells.
Reversing Metabolic Shift: It suppresses the Warburg effect by forcing pyruvate to enter the mitochondria for conversion into acetyl-CoA, rather than being converted into lactic acid in the cytoplasm.
Molecular Targets: Melatonin downregulates key metabolic pathways, including the pentose phosphate pathway, and inhibits HIF-1
, a transcription factor that drives glycolysis.By forcing cancer cells to return to a more normal metabolic state, melatonin reduces their survival and proliferation, making it a promising candidate for adjuvant therapy in cancer treatment.
Melatonin redirects pyruvate from lactate production in the cytosol to mitochondrial acetyl-CoA formation, reversing aerobic glycolysis in cancer cells like hepatocellular carcinoma (HuH 7.5) and ovarian cancer (SKOV-3). This reduces glucose uptake, lactate dehydrogenase activity, and cell proliferation while enhancing oxidative phosphorylation. In Ewing sarcoma models, it inhibits HIF-1α-driven glycolysis, sparing non-Warburg cells.
Melatonin lowers elevated lactate-to-pyruvate ratios in stress-induced muscle atrophy by curbing oxidative stress and boosting Na+/K+ ATPase activity. It boosts lactate-to-pyruvate interconversion and cuts lactate output in cancer lines, independent of MT1 receptors in some cases.These shifts support metabolic health beyond oncology, like in retinal ischemia.Just a few studies
https://pmc.ncbi.nlm.nih.gov/articles/PMC7828708/https://pubmed.ncbi.nlm.nih.gov/36863486/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135420
This could be a strong reason behind why having an optimal circadian rythm lowers cancer risk