title: 10-acetylirciformonin B, a sponge furanoterpenoid, induces DNA damage and apoptosis in leukemia cells.
abstract: 10-Acetylirciformonin B, a furanoterpenoid derived from irciformonin B found in a marine sponge, has been reported to possess potent cytotoxic activity against several cancer cell lines. However, the mechanism of its apoptotic activity against human leukemia cells has never been reported. The purpose of this study was to investigate the cytotoxic effects of 10-acetylirciformonin B and its possible mechanism of action against leukemia HL 60 cells. We found that 10-acetylirciformonin B decreased cell viability through the inhibition of cell growth as well as the induction of DNA damage and apoptosis in a dose-dependent manner. The induction of DNA damage was mediated by the increase of p-CHK2 and γ-H2A.X, which was suggested from the increase of tail movement in the neutral Comet assay. Induction of apoptosis was mediated with the increase in caspases 8, 9 and 3 activation as well as PARP cleavage. In summary, our resultsindicate that 10-acetylirciformonin B treatment causes apoptosis in leukaemia cells; probably through a caspase-dependent regulatory pathway.
authors.affiliation: Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan.
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.forename: Wen-Been
authors.initials: WB
authors.lastname: Chang
authors.forename: Huei-Mei
authors.initials: HM
authors.lastname: Chen
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Shazly
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Du
authors.forename: Ting-Hsuan
authors.initials: TH
authors.lastname: Kung
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Yuan-Shing
authors.initials: YS
authors.lastname: Ho
authors.forename: Fu-Wen
authors.initials: FW
authors.lastname: Kuo
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011161:Porifera / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C562206:10-acetylirciformonin B; D000970:Antineoplastic Agents; D013729:Terpenes; D020169:Caspases