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^[1]. 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^[2].

The cytotoxicity of sesamol on HepG2 cells and BRL-3A cells is examined by using MTT assay. Briefly, cells in exponential growth are seeded into 96-well plates at a density of 1 × 10⁵ cells/mL. The cells are then treated with sesamol at various doses (0, 0.01, 0.05, 0.1, 0.2, 0.5 or 1 mM). After 24 h, the supernatant is discarded and 100 μL FBS free medium is added. 100 μL of MTT is added in each well, and cells are further incubated for 4 h in the dark. After incubation, the medium is discarded, 100 μL of DMSO is added, and the optical density of each well is measured at 570 nm.

Sesamol has potent anti-hepatoma activity in a xenograft nude mice model^[1].