Benzyldihydroxyoctenone, a novel nonsteroidal antiandrogen, shows differential apoptotic induction in prostate cancer cells in response to their androgen responsiveness.

Abstract

The molecular mechanisms of apoptotic induction by benzyldihydroxyoctenone (BDH), a nonsteroidal antiandrogen, isolated from the culture broth of Streptomyces sp., have been previously published in prostate cancer LNCaP cells. Apoptotic induction of BDH-treated LNCaP cells was associated with downregulation of Bcl-xL that caused, in turn, cytochrome c release from mitochondria, and activation of procaspases and specific proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). The purpose of the present study was to investigate the patterns of apoptotic induction by BDH in non-prostate, ovarian cancer PA-1 (androgen-independent and -insensitive) cells and prostate cancer cells with different androgen responsiveness, such as C4-2 (androgen-independent and -sensitive), 22Rv1 (androgen-dependent and -low sensitive), and LNCaP (androgen-dependent and -high sensitive) cells. We found that BDH-treated LNCaP cell proliferation was significantly inhibited in a time-dependent manner and induced apoptosis via downregulation of the androgen receptor (AR) and prostate-specific antigen (PSA), as well as antiapoptotic Bcl-xL protein. However, the levels of BDH-mediated apoptotic induction and growth inhibition in 22Rv1 cells were apparently lower than those of LNCaP cells. In contrast, the induction of apoptosis and antiproliferative effect in BDH-treated non-prostate cancer PA-1 and hormone refractory C4-2 cells were not detectable and marginal, respectively. Therefore, BDH-mediated differential apoptotic induction and growth inhibition in a cell type seem to be obviously dependent on its androgen responsiveness; primarily on androgen-dependency, and then on androgen sensitivity.

• Authors: Hyewon Suh, Ha Lim Oh, Chul-Hoon Lee
• Journal: Journal of microbiology and biotechnology (J Microbiol Biotechnol) Vol. 21 Issue 5 Pg. 540-4 (May 2011) ISSN: 1738-8872 [Electronic] Korea (South)
• PMID: 21617354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Androgens
• Octanols
• Receptors, Androgen
• benzyldihydroxyoctenone
• Prostate-Specific Antigen

Topics

• Androgen Antagonists (pharmacology)
• Androgens (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Octanols (pharmacology)
• Prostate-Specific Antigen (genetics, metabolism)
• Prostatic Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Receptors, Androgen (genetics, metabolism)