Apoptotic and antiapoptotic effect of (-)deprenyl and (-)-desmethyl-deprenyl on human cell lines.
The antiapoptotic effect of (-) deprenyl on human phaeochromocytoma cells after serum deprivation has been reported by earlier. Two melanoma (M-1 and HT-2058) cell lines were used in our experiments. Serum deprivation for five days resulted in excessive number of apoptosis in the cell cultures. Very low doses of (-)-deprenyl (10(-7)-10(-13) mol) caused an approximately 2 days delay in the onset of apoptosis. At the same time, +deprenyl was ineffective. In further experiments (-)-deprenyl and (-)desmethyl-deprenyl was administered in higher doses (10(-2), 10(-3) and 10(-4) mol) to A-2058 melanoma and HT-1080 fibrosarcoma cells in culture. In these experiments no serum deprivation was applied and the treatment was started 24 hours after plating. Total eradication of the A-2058 cells was caused by 10(-2) mol (-)-deprenyl and (-)-desmethyl-deprenyl. The type of cell death appeared to be apoptosis. Sixty percent apoptotic ratio was seen 24 hours and 72 hours after 10(-3) mol (-)-desmethyl-deprenyl treteatment. The same dose of (-)-deprenyl caused 50% apoptosis an 72 h. Only (-)-desmethyl-deprenyl induced apoptosis (20%) at 24 hours, in the dose of 10(-4) mol. Interestingly (-)-deprenyl treatment resulted in 60% apoptosis.
1st Institute of Pathology and Experimental Cancer Research and Molecular Pathology, Research Group of the National Academy of Sciences, Semmelweis University of Medicine, Budapest, Hungary.
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Szende
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Magyar
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Szegedi
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000662:Amphetamines; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; C017861:desmethylselegiline