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.
Department of Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brigadier SK Mazumdar Marg, Timarpur, New Delhi 110 054, India.
P K
PK
Agrawala
A
A
Mittal
M
M
Bala
H C
HC
Goel
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D011035:Podophyllum; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D027343:Rhizome
D000970:Antineoplastic Agents; D005609:Free Radicals; D018840:HSP70 Heat-Shock Proteins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2