title: Involvement of cholesterol depletion from lipid rafts in apoptosis induced by methyl-β-cyclodextrin.
abstract: Methyl-β-cyclodextrin (M-β-CyD), which is widely used as a lipid rafts disrupting agent, is known to induce cytotoxicity at high concentration. In the present study, we investigated the potential of M-β-CyD as an antitumor drug. M-β-CyD markedly caused apoptotic cell-death in KB cells, a human oral squamous carcinoma cell line, Ihara cells, a highly pigmented human melanoma cell line, and M213 cells, a human cholangiocarcinoma cell line, through cholesterol depletion in cell membranes. The DNA content and mitochondrial transmembrane potential in KB cells were significantly decreased after treatment with M-β-CyD. Additionally, M-β-CyD elevated the caspase-3/7 activity in KB cells. Meanwhile, M-β-CyD did not induce the formation of autophagic vacuoles in KB cells. M-β-CyD drastically inhibited the tumor growth after intratumoral injection to Colon-26 cells-bearing mice. These results strongly suggest that M-β-CyD induced apoptosis in tumor cells and had the potential a novel antitumor agent and/or its lead compound.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Onodera
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Ayaka
authors.initials: A
authors.lastname: Okamatsu
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D004247:DNA; D002784:Cholesterol; D053148:Caspase 3; D053179:Caspase 7