[CAS NO. 533-31-3]  Sesamol

Sesamol treatment suppresses colony formation, elicits S phase arrest during cell cycle progression, and induces both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicits mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production results in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis is inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibits mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reverses sesamol-induced apoptosis and mitochondrial respiration disorders. Sesamol increases the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol causes the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction in human lung adenocarcinoma (SK-LU-1) cells.