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Investigation of anticancer mechanism of clavulone II, a coral cyclopentenone prostaglandin analog, in human acute promyelocytic leukemia

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Journal of Biomedical Science

Summary

The marine prostanoid clavulones were shown to exert cytotoxicity against several cancer cells. In the present study, we illustrate the pathways utilized by clavulone II to trigger apoptotic signaling in human acute promyelocytic leukemia HL-60 cells. Exposure of cells to clavulone II resulted in early induction of phosphatidylserine externalization, mitochondrial dysfunction, and alteration of the cell cycle. Down-regulated expression of cyclin D1 explained the effect of clavulone II on G1 phase arrest of the cell cycle. Clavulone II induced the disruption of mitochondrial membrane potential and activation of caspase-8, -9 and -3 in a time- and concentration-dependent manner. Furthermore, the effect of 3 μM clavulone II was accompanied by the up-regulation of Bax, down-regulation of Mcl-1, and cleavage of Bid. Taken together, it is suggested that low concentrations of clavulone II induce the antiproliferative effect through the down-regulation of cyclin D1 expression and G1 arrest of the cell cycle, while that of high concentration induce the apoptotic cell death via the modulation of members of caspases and Bcl-2 family proteins in HL-60 cells.

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Authors and Affiliations

  1. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan

    Yu-Chun Huang & Che-Ming Teng

  2. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

    Jih-Hwa Guh

  3. Institute of Marine Resources, National Sun Yat-sen University, Kaohsiung, Taiwan

    Ya-Ching Shen

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  1. Yu-Chun Huang
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  2. Jih-Hwa Guh
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  3. Ya-Ching Shen
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  4. Che-Ming Teng
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Correspondence to Che-Ming Teng.

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Huang, YC., Guh, JH., Shen, YC. et al. Investigation of anticancer mechanism of clavulone II, a coral cyclopentenone prostaglandin analog, in human acute promyelocytic leukemia. J Biomed Sci 12, 335–345 (2005). https://doi.org/10.1007/s11373-005-3009-9

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  • DOI: https://doi.org/10.1007/s11373-005-3009-9

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