Induction of Fas clustering and apoptosis by coral prostanoid in human hormone-resistant prostate cancer cells

Po Cheng Chiang, Fan Lu Kung, Dong Ming Huang, Tsai Kun Li, Jia Rong Fan, Shiow Lin Pan, Ya Ching Shen, Jih Hwa Guh

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22 Citations (Scopus)

Abstract

Cyclopentenone prostaglandins (PGs) such as PGA1, PGA2 and Δ12-PGJ2 have been shown to suppress tumor cell growth and to induce apoptosis in prostate cancer cells. Bromovulone III, which is isolated from the soft coral Clavularia viridis, is a cyclopentenone prostanoid. In this study, the anti-tumor activity as well as action mechanism of bromovulone III was identified in prostate cancer cells. Bromovulone III displayed anti-tumor activity of 30 to 100 times more effective than PGA1, PGA2 and Δ12-PGJ2 in PC-3 cells. Several targets of caspases and Bcl-2 family of proteins were detected and the data demonstrated that bromovulone III induced the activation of caspase-8, -9 and -3, and Bid cleavage in which the caspas-8 activation occurred the first. Bromovulone III did not modify the protein levels of death receptors and ligands. Of note, the Fas clustering in PC-3 cells responsive to bromovulone III was observed by confocal immunofluorescence microscopy suggesting the involvement of Fas-mediated pathway. Bromovulone III also induced the cleavage of Mcl-1 in this study. The cleavage fragments (24, 19 and 17 kDa) may partly share the apoptotic insult. Although it has been suggested that Fas-mediated signaling may contribute to the caspase-8 activation induced by DNA-damaging agents; however, bromovulone III did not induce any DNA breakage, suggesting that bromovulone III-induced Fas/caspase-8-dependent signaling is not through the direct target on DNA damage. In summary, the data suggest that bromovulone III causes a rapid redistribution and clustering of Fas in PC-3 cells. Subsequently, the Fas event causes the activation and interaction of caspase-8/Bid/caspase-9 signaling cascades, and the activation of executor caspase-3.

Original languageEnglish
Pages (from-to)22-30
Number of pages9
JournalEuropean Journal of Pharmacology
Volume542
Issue number1-3
DOIs
Publication statusPublished - Aug 7 2006
Externally publishedYes

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Keywords

  • Fas clustering
  • Mcl-1 cleavage
  • Prostanoid
  • Prostate cancer

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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