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

Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Korea.

 

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 androgensensitivity.

Written by:
Suh H, Oh HL, Lee CH.   Are you the author?

Reference: J Microbiol Biotechnol. 2011 May;21(5):540-4.

PubMed Abstract
PMID: 21617354

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