Gamma-tocopherol enhances apoptotic effects of lovastatin in human colorectal carcinoma cell line (HT29).

Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of the significant types of vitamin E in diet, additively induced apoptosis in a colorectal carcinoma cell line. In this study we mechanistically monitored the loss of mitochondrial membrane potential, amount of cytosolic cytochrome c and caspase 3 activity after treatment by lovastatin and gamma-tocopherol. HT29 cells were treated with different doses of lovastatin and gamma-tocopherol for 48 and 72 h. Lovastatin and gamma-tocopherol in combination induced the release of cytochrome c, caspase 3 activation, and loss of mitochondrial membrane potential more significantly compared to their controls. Our data showed that lovastatin plus gamma tocopherol potently induced mitochondrial membrane potential collapse, cytochrome c release along with caspase 3 activation that reveals the importance of targeting programmed cell death signaling at different points of its signaling pathway for cancer therapy.