Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells

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 I kappa B alpha in PC-3 cells, which was associated with the inhibition of proteasome activity. Taken together, capsaicin inhibits proteasome activity which suppressed the degradation Of I kappa B alpha, preventing the activation of NF-kappa B. 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 suggests that capsaicin, or a related analogue, may have a role in the management of prostate cancer.