AMPK and Cancer
AMPK activation inhibits mTORC1 signaling, which leads to inhibition of translation of many proteins required for rapid cell growth. AMPK activation also inhibits the synthesis of most cellular macromolecules, including fatty acids, triglycerides, cholesterol, glycogen, ribosomal RNA and proteins which in turn inhibit cell growth. AMPK activation also causes cell cycle arrest by stabilizing p53 and the cyclin-dependent kinase inhibitors p21WAF1 and p27CIP1. In addition, AMPK activation supresses the Warburg effect which is the switch away from oxidative metabolism and towards rapid glucose uptake and glycolysis characteristic of most tumour cells.
O304 exhibits multiple direct and indirect anti-tumour effects
O304 inhibits the proliferation of multiple tumour cell lines as well as of primary human acute myeloid leukaemia cells and primary acute T-cell lymphoma cells. Under these conditions, O304 inhibits mTORC1 signaling and lipid synthesis. O304 also reduces diet-induced hyperinsulinemia and plasma IGF-1 levels in animals which may indirectly reduce mTORC1 signaling and tumour cell growth and proliferation.