Downregulation of survivin expression and elevation of caspase-3 activity involved in pitavastatin-induced HepG 2 cell apoptosis.
The aim of the present study was to research the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin. HepG 2 cells were treated with increasing doses of pitavastatin or with mevalonic acid for 48 h. The proliferation of cells was detected with WST-8. The morphology of the nucleus was observed under a microscope by Hoechst 33258 staining. The apoptosis peaks were examined by flow cytometry. The expression of survivin mRNA was examined with RT-PCR. The caspase-3 activity was detected with caspase-3 colorimetric protease assay. We found that growth inhibitory effects were observed for treatment with pitavastatin at 10-50 microM. Pitavastatin at 10 microM induced granular apoptotic bodies of HepG 2 cells. Furthermore, pitavastatin at 10 microM increased the appearance of sub-G1 population of HepG 2 cells. Finally, pitavastatin at 10 microM downregulated the expression of survivin mRNA and upregulated the caspase-3 activity, which was clearly related to the HMG-CoA reductase activity. These results suggest that pitavastatin at 10 microM induces apoptosis of HepG 2 cells, which is associated with the decreased expression of survivin mRNA and increased caspase-3 activity of HepG 2 cells.
Wang
Juyong
J
Tumor Research Institute, Shanghai Academy of Traditional Chinese Medicine, Shanghai 200032, PR China. wangjuyong1@126.com
Xu
Zhenye
Z
Zhang
Ming
M
D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins; D008798:Mevalonic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011804:Quinolines; D012333:RNA, Messenger; D000077022:Survivin; D053148:Caspase 3; D006690:Bisbenzimidazole; C108475:pitavastatin; D008798:Mevalonic Acid