ABSTRACT
The tocotrienols, at physiologically attainable concentrations, arrest the in vitro growth of cell lines derived from broadly diverse human and animal tumors and, at several fold higher concentrations, the growth of physiologically normal cells. Preclinical studies demonstrate the suppression of the growth of implanted tumors, absent an impact on the growth of the host and of carcinogenesis initiated by diverse carcinogens. The tocotrienol-mediated suppression of cell growth, an action involving both the accumulation of cells in the G1 phase of the cell cycle and the initiation of apoptosis, is reversed by supplemental mevalonate or specic mevalonate-derived products. It therefore appears reasonable to attribute the chemoprotective actions of the tocotrienols to the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, a dysregulated activity in tumor cells that retains sensitivity to the posttranscriptional down regulation triggered by the tocotrienols. In support of this reasoning, parallels are drawn between the impacts of statins and tocotrienols on components of signaling networks that modulate cell cycle, anti-apoptotic and apoptotic activities.
