10-acetylirciformonin B, a sponge furanoterpenoid, induces DNA damage and apoptosis in leukemia cells

• Published in: Molecules (Basel, Switzerland) Vol. 17; no. 10; pp. 11839 - 11848
• Main Authors: Su, Jui-Hsin, Chang, Wen-Been, Chen, Huei-Mei, El-Shazly, Mohamed, Du, Ying-Chi, Kung, Ting-Hsuan, Chen, Yu-Cheng, Sung, Ping-Jyun, Ho, Yuan-Shing, Kuo, Fu-Wen, Lu, Mei-Chin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.10.2012; MDPI
• Subjects: 10-acetylirciformonin B; Alzheimer's disease; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Ataxia; Cancer; Caspases - metabolism; Cell cycle; Cell growth; Cell Proliferation - drug effects; Cytotoxicity; DNA Breaks, Double-Stranded - drug effects; DNA damage; DNA Damage - drug effects; Drug dosages; HL-60 Cells; Humans; Inhibitory Concentration 50; Kinases; Leukemia; Marine biology; Metabolites; Natural products; Pharmacy; Phosphorylation; Porifera - chemistry; Signal Transduction - drug effects; sponge; Terpenes - pharmacology; Terpenes - toxicity; Toxicity; Taiwan
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules171011839

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.