Induction of a reversible, non‐cytotoxic S‐phase delay by resveratrol: implications for a mechanism of lifespan prolongation and cancer protection

摘要: Background and purpose:  Resveratrol (RES) has been shown to prolong lifespan prevent cancer formation. At present, the precise cellular mechanisms of RES actions are still not clearly understood, this is focus study. Experimental approach:  Using human hepatocellular carcinoma-derived HepG2 cells as a model, we studied RES-induced changes in cell growth, cycle progression apoptosis. Key results:  at lower concentrations induced strong but reversible S-phase delay mild DNA synthesis inhibition, yet without causing apoptotic or necrotic death. high concentrations, apoptosis, which mainly mediated by mitochondrial pathway. Overall, was relatively weak agent. Mechanistically, MEK inhibition identified an important early signalling event for apoptosis. In comparison, activation CDK2 checkpoint kinase 2, phosphatidylinositol 3′-kinase/Akt pathway contributed induction reversible, non-cytotoxic delay. Conclusion implications:  It hypothesized that may represent useful mechanistic strategy prolongation prevention. When cycles selectively slowed down S phase, it would cumulatively increase total organism if numbers divisions given assumed remain basically constant. Likewise, when proceed through reduced pace during replication, allow more time repair damaged DNA, thereby reduce chances mutagenesis tumour initiation.