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.
Agrawala
P K
PK
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.
Mittal
A
A
Bala
M
M
Goel
H C
HC
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