A Combination of Moringin and Avenanthramide 2f Inhibits the Proliferation of Hep3B Liver Cancer Cells Inducing Intrinsic and Extrinsic Apoptosis

Moringin (MOR), a glycosyl-isothiocyanate obtained by myrosinase-catalyzed hydrolysis of the precursor 4-(-l-rhamnosyloxy)-benzyl glucosinolate (glucomoringin), found predominantly in the seeds of Moringa oleifera, shows anticancer effects against several cancer cell lines. Avenanthramide (AVN) 2f is a phytochemical purified from oats with antioxidant and anticancer properties. The aim of this study was to investigate the antiproliferative and proapoptotic effects of MOR and AVN 2f used alone and in combination on Hep3B cancer cells, which are highly resistant to conventional anticancer drugs. We found that a cocktail of MOR and AVN 2f significantly inhibited the Hep3B proliferation rate by markedly increasing the activity of caspases 2, 8, 9, and 3. Extrinsic apoptosis was induced by the AVN 2f-mediated activation of caspase 8, while the intrinsic apoptotic pathway was triggered by MOR-induced increase in the levels of intracellular reactive oxygen species, MOR-mediated activation of caspases 2 and 9 and the MOR-mediated downregulation of the prosurvival gene BIRC5. Our results suggest that the combination MOR+AVN 2f could be an effective chemopreventive cocktail against the development of hepatocarcinoma.