Hesperetin induces an apoptosis-triggered extrinsic pathway and a p53- independent pathway in human lung cancer H522 cells.

We studied the chemoprevention property of hesperetin on H522 cells using MTT, an apoptosis assay, an analysis of cell cycle progression, and the mitochondrial membrane potential, and apoptotic marker gene expression was determined using quantitative PCR. Hesperetin enhanced apoptotic cell death and mitochondrial membrane potential loss in H522 cells. Hesperetin up-regulated the levels of Fas, FADD, and caspase-8 expression and downregulted the levels of caspase-3 and caspase-9, p53, and Bax expression in H522 cells. This study shows that hesperetin induces apoptosis in H522 cells via a pathway independentof p53 and Bax but triggers the death-receptor Fas-initiated FADD/ caspase-8-dependent apoptotic pathway.