tailieunhanh - báo cáo khoa học: " Statin-induced apoptosis via the suppression of ERK1/2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Statin-induced apoptosis via the suppression of ERK1/2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma | Yanae et al. Journal of Experimental Clinical Cancer Research 2011 30 74 http content 30 1 74 Journal of Experimental Clinical Cancer Research RESEARCH Open Access Statin-induced apoptosis via the suppression of ERK1 2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma 1 3 3 4 5 Masashi Yanae 1 Masanobu Tsubaki Takao Satou Tatsuki Itoh Motohiro Imano Yuzuru Yamazoe and Shozo Nishida1 Abstract Background Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase the rate-limiting enzyme in cholesterol synthesis. The inhibition of this key enzyme in the mevalonate pathway leads to suppression of cell proliferation and induction of apoptosis. However the molecular mechanism of apoptosis induction by statins is not well understood in glioblastoma. In the present study we attempted to elucidate the mechanism by which statins induce apoptosis in C6 glioma cells. Methods The cytotoxicity of statins toward the C6 glioma cells were evaluated using a cell viability assay. The enzyme activity of caspase-3 was determined using activity assay kits. The effects of statins on signal transduction molecules were determined by western blot analyses. Results We found that statins inhibited cell proliferation and induced apoptosis in these cells. We also observed an increase in caspase-3 activity. The apoptosis induced by statins was not inhibited by the addition of farnesyl pyrophosphate squalene ubiquinone and isopentenyladenine but by geranylgeranyl-pyrophosphate GGPP . Furthermore statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1 2 ERK1 2 and Akt. Conclusions These results suggest that statins induce apoptosis when GGPP biosynthesis is inhibited and consequently decreases the level of phosphorylated ERK1 2 and Akt. The results of this study also indicate that statins could be used as anticancer agents in glioblastoma. Keywords statins C6 glioma ERK Akt Background .