S-benzyl-cysteine-mediated Cell Cycle Arrest and Apoptosis Involving Activation of Mitochondrial-dependent Caspase Cascade through the p53 Pathway in Human Gastric Cancer SGC-7901 Cells

Abstract

S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major watersolublecompounds in aged garlic extract. In this study, anticancer activities and the underlying mechanismsof SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependentmanner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBCinduced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observedby Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membranepotential (ΔΨm), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affectingcaspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied byup-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggestedthat SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 andBax/Bcl-2 pathways in human gastric cancer SGC-7901 cells.

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