Mitochondrial involvement in RP-1 mediated apoptosis in U 87 cells

The aqueous extract of RP-1, which rendered significant protection to whole body irradiated mice, was found to be tumoricidal. The mode of cytotoxic action of RP-1 attributing to its antitumor action was investigated in U 87 cells with special reference to mitochondrial contribution. RP-1 doses above 0.5 microg/ml reduced colonogenic survival (maximum reduction of 62% at 10 microg/ml) and increased the free radical generation, G2/M fraction and apoptotic frequency. Prolonged exposure to RP-1 rendered significant increase in mitochondrial mass. It also reduced mitochondrial membrane potential in a dose and time dependent manner that was restored by verapamil, a Ca+2 channel blocker. Mitochondrial anti-apoptotic proteins Bcl-2 and Hsp-70 levels were also reduced by RP-1 treatment in a dose and time dependent manner. The ability of RP-1 to disrupt mitochondrial structure and function could be responsible for its cytotoxic action.