Abstract A34: Cholesterol depletion in cell membrane induces apoptosis of oral cavity cancer cells

Abstract

Abstract Cell membrane cholesterol is not distributed evenly, but it mainly exists in a specific microdomain of cell membrane called lipid raft. The lipid rafts consist of cholesterol and glycosphingolipid, and are associated with the regulation of transmembrane receptors. Cholesterol depletion has been reported to bring structural disruption of the raft and functional change of associated receptors which leads to the induction of apoptosis in certain types of cells. In this study, the cell membrane cholesterol of oral cavity cancer cells such as SCC-15, SCC-25, and SCC-QLL1 cell line was depleted by treating with methyl β-cyclodextrin (MβCD), and the effect of cholesterol depletion on the induction of apoptosis was evaluated. Treating oral cavity cancer cells for 1 hour with 1% MβCD inhibited cell proliferation. The cholesterol analysis and the filipin fluorescence staining demonstrated that MβCD selectively depleted cholesterol in oral cavity cancer cells. Furthermore, flow cytometry, poly (ADP-ribose) polymerase (PARP) cleavage assay, ELISA cell death assay showed that this inhibition of cell proliferation was caused by apoptosis. To evaluate the relationship between Mitogen-activated protein kinases (MAPK) and this apoptosis, Western blot analysis of the oral cavity cancer cells treated with MβCD was performed using the antibodies of Phospho-Extracellular signal-regulated kinase (p-ERK), phospho-p38 MAPK, and phosho-Jun-N-terminal kinases (p-JNK). The activity of ERK, p38 MAPK, and JNK in each oral cavity cancer cells was changed after treating with MβCD. In conclusion, cholesterol depletion of cell membrane may be considered as one of treatment modalities for oral cavity cancer, but further studies on its mechanism will be needed. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A34.