Downregulation of survivin expression and elevation of caspase-3 activity involved in pitavastatin-induced HepG 2 cell apoptosis

Abstract

Abstract. 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 μM. Pitavastatin at 10 μM induced granular apoptotic bodies of HepG 2 cells. Furthermore, pitavastatin at 10 μM increased the appearance of sub-G1 population of HepG 2 cells. Finally, pitavastatin at 10 μM 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 μM 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.

Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin

“…Previous studies only described survivin down-regulation itself by statin [18,19]. Our result demonstrates more specific and detailed mechanism than the prior reports.…”

“…Recently, considerable evidence has suggested that statininduced apoptosis is associated with down-regulation of survivin expression in cancer cells [19]. However, the mechanism underlying deregulated survivin by simvastatin on human non-small cell lung cancer cells has not been elucidated.…”

Tanshinone IIA acts via p38 MAPK to induce apoptosis and the down-regulation of ERCC1 and lung-resistance protein in cisplatin-resistant ovarian cancer cells

“…Previous data have revealed that survivin is one of the genes most consistently over-expressed in tumor cells and plays important roles in both cell proliferation and cell death (30). Downregulation of survivin expression may lead to programmed cell death (31), indicating that it may be an appealing new target for novel therapy in cancer (32). Our results show that tanshinone IIA may trigger apoptosis in COC1/DDP cells by downregulating survivin levels via activation of p38 MAPK.…”

Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to activation of Bax and down-regulation of BCL-2 gene expression

“…Apoptosis plays a key role in the pathogenesis of cancers and the genes relating to this process are focus of interest in the studies of cancer onset and progression. It is well-known that Bax and BCL-2 are transcriptional targets for the tumor suppression protein p53 (17), which is responsible for the induction of cell cycle arrest and/or apoptosis in response to DNA damage (21). …”