Study of Mechanism of Lovastatin-induced Apoptosis in Oral Cancer Ca9-22 cells.
Date Issued
2009
Date
2009
Author(s)
Wu, Fang-Yi
Abstract
Oral cancer is the fifth leading cause of cancer-related deaths in male population in Taiwan. Despite recent advances in radiotherapy and chemotherapy, the survival of patients with oral cancer has not improved significantly. Continues investigation of new chemotherapeutic agents is need. The 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors, also known as statins, are commonly prescribed medications that lower serum cholesterol. Preclinical research performed during the past decade shows that statins have antineoplastic effects in many tumor cell lines. Therefore, we were interested in exploring the potential of lovastatin as an anti-cancer agent in oral cancer cells. We found lovastatin significantly inhibited the cell proliferation of Ca9-22 in a dose-dependent manner. Flow cytometric analysis of DNA content showed that lovastatin treatment induced apoptosis following G1 arrest. Western blotting showed lovastatin increased cytochrome c release and activated caspase-8 and caspase-9. Caspase-9 activation is earlier than caspase-8. The apoptosis could be inhibited by caspase 8 inhibitor (Z-LEHD-FMK) or caspase 9 inhibitor (Z-IETD-FMK). These results demonstrated that the intrinsic apoptotic pathway may play a major role in the lovastatin-induced apoptosis. Pretreatment of cells with N-acetyl cysteine (NAC), MAPKs inhibitors and PI3K/Akt inhibitors inhibited the PARP cleavage. MAPKs, PI3K/Akt pathway and ROS may play important roles in lovastatin-induced apoptosis. Taking together, the chemopreventive potential of lovastatin is required to be further determined with animal model and clinical trails in the future.
Subjects
Lovastatin
Aapoptosis
Oral cancer
SDGs
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