Szende B, Magyar K, Szegedi Z
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.
Neurobiology (Bp). 2000;8(3-4):249-55.
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.
早期已有报道称（-）司来吉兰对血清剥夺后的人嗜铬细胞瘤细胞具有抗凋亡作用。我们的实验使用了两种黑色素瘤（M-1和HT-2058）细胞系。血清剥夺五天导致细胞培养物中出现过多的凋亡细胞。极低剂量的（-）-司来吉兰（10^(-7)-10^(-13)摩尔）使凋亡开始时间延迟了约两天。同时，（+）-司来吉兰无效。在进一步的实验中，将（-）-司来吉兰和（-）-去甲基司来吉兰以更高剂量（10^(-2)、10^(-3)和10^(-4)摩尔）施用于培养中的A-2058黑色素瘤细胞和HT-1080纤维肉瘤细胞。在这些实验中未进行血清剥夺，且在接种后24小时开始治疗。10^(-2)摩尔的（-）-司来吉兰和（-）-去甲基司来吉兰导致A-2058细胞完全消除。细胞死亡类型似乎是凋亡。10^(-3)摩尔（-）-去甲基司来吉兰处理后24小时和72小时观察到60%的凋亡率。相同剂量的（-）-司来吉兰在72小时时导致50%的凋亡。仅10^(-4)摩尔剂量的（-）-去甲基司来吉兰在24小时时诱导20%的凋亡。有趣的是，（-）-司来吉兰处理导致60%的凋亡。
