Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor.

Journal of Biomedical Science
Srinivas RajamahantySensuke Konno

Abstract

Androgen ablation is one of the viable therapeutic options for patients with primary hormone (androgen)-dependent prostate cancer. However, an antibiotic brefeldin A (BFA) has been shown to exhibit the growth inhibitory effect on human cancer cells. We thus investigated if BFA might inhibit proliferation of androgen-responsive prostate cancer LNCaP cells and also explored how it would be carried out, focusing on cell cycle and androgen receptor (AR). Androgen-mediated cellular events in LNCaP cells were induced using 5alpha-dihydrotestosterone (DHT) as an androgenic mediator. Effects of BFA on non-DHT-stimulated or DHT-stimulated cell growth were assessed. Its growth inhibitory mechanism(s) was further explored; performing cell cycle analysis on a flow cytometer, assessing AR activity by AR binding assay, and analyzing AR protein expression using Western blot analysis. DHT (1 nM) was capable of stimulating LNCaP cell growth by ~40% greater than non-stimulated controls, whereas BFA (30 ng/ml) completely inhibited such DHT-stimulated proliferation. Cell cycle analysis showed that this BFA-induced growth inhibition was associated with a ~75% reduction in the cell number in the S phase and a concomitant increase in the G1 cell numb...Continue Reading

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Citations

Aug 27, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chao-Neng TsengYung-Fu Chang
Jul 14, 2012·European Journal of Medicinal Chemistry·Robert G BrittonStewart Sale
Jul 20, 2017·Natural Product Research·Xiangwei ChengZhongjun Ma
Jun 5, 2019·The Kaohsiung Journal of Medical Sciences·Ai-Guo MaQing Wang
Jan 9, 2019·Frontiers in Pharmacology·Yiming ChenLei Zhang
Aug 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jin-Man ZhangMing Liu

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Methods Mentioned

BETA
protein assay
electrophoresis
X-ray

Software Mentioned

CellFit

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