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

• Published in: Biomedicine & pharmacotherapy 2004-03, Vol.58 (2), p.129-135
• Main Authors: Agrawala, P.K., Mittal, A., Bala, M., Goel, H.C.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Dose-Response Relationship, Drug; Free Radicals - metabolism; G 2/M arrest; HSP70 Heat-Shock Proteins - biosynthesis; Humans; Medical sciences; Membrane Potentials; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - physiology; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Podophyllum; Podophyllum hexandrum; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Rhizome
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2003.10.002

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 μg/ml reduced colonogenic survival (maximum reduction of 62% at 10 μg/ml) and increased the free radical generation, G 2/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.