Capsaicin, a Component of Red Peppers, Inhibits the Growth of Androgen-Independent, p53 Mutant Prostate Cancer Cells

作者：Akio Mori, Sören Lehmann, James O’Kelly, Takashi Kumagai, Julian C. Desmond, Milena Pervan, William H. McBride, Masahiro Kizaki, H. Phillip Koeffler · 发表于：Cancer Research · 年份：2006 · DOI：10.1158/0008-5472.can-05-0087 · 被引用次数：400 · 研究领域：Ion Channels and Receptors、NF-κB Signaling Pathways、Cell death mechanisms and regulation

Capsaicin is the major pungent ingredient in red peppers. Here, we report that it has a profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and -negative (PC-3, DU-145) prostate cancer cell lines associated with an increase of p53, p21, and Bax. Capsaicin down-regulated the expression of not only prostate-specific antigen (PSA) but also AR. Promoter assays showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA promoter/enhancer even in the presence of exogenous AR in LNCaP cells, suggesting that capsaicin inhibited the transcription of PSA not only via down-regulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-kappa activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-alpha-stimulated degradation of IkappaBalpha in PC-3 cells, which was associated with the inhibition of proteasome activity. Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha, preventing the activation of NF-kappaB. Capsaicin, when given orally, significantly slowed the growth of PC-3 prostate cancer xenografts as measured by size [75 +/- 35 versus 336 +/- 123 mm(3) (+/-SD); P = 0.017] and weight [203 +/- 41 versus 373 +/- 52 mg (+/-SD); P = 0.0006; capsaicin-treated versus vehicle-treated mice, respectively]. In summary, our data su...