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

Abstract

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 downregulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-K activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-A-stimulated degradation of IKBA in PC-3 cells, which was associated with the inhibition of proteasome activity. Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IKBA, preventing the activation of NF-KB. Capsaicin, when given orally, significantly slowed the growth of PC-3 prostate cancer xenografts as measured by size [75 F 35 versus 336 F 123 mm 3 (FSD); P = 0.017] and weight [203 F 41 versus 373 F 52 mg (FSD); P = 0.0006; capsaicin-treated versus vehicletreated mice, respectively]. In summary, our data suggests that capsaicin, or a related analogue, may have a role in the management of prostate cancer. (Cancer Res 2006; 66(6): 3222-9)

Estonian folk traditional experiences on natural anticancer remedies: From past to the future

“…A pungent bioactive ingredient in varieties of Capsicum annuum (red pepper) is capsaicin and its antitumor activities have reported in various malignant cells, such as human esophageal, gastric, cervical, ovarian, breast, prostate, and liver carcinoma as well as leukemia and melanoma cells (Huang et al, 2009;Lo et al, 2005;Mori et al, 2006;Wu et al, 2006;Zhang et al, 2003). In the case of prostate cancer, capsaicin can inhibit both androgen-sensitive and -insensitive tumors pointing to its potential role in the management of prostate cancer patients, refractory to hormonal therapies (Mori et al, 2006). At the same time, the root extract of Beta vulgaris L. (Chenopodiaceae) (beet) can inhibit the growth of hormone-dependent human breast cancer cells (Tripathy & Pradhan, 2013) and taproot juice of Daucus sativus Hort.…”

Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species

“…Capsaicinoids have been found in nature to have antifungal and antibacterial properties, to act as a deterrent to animal predation when ingested and to have inherent properties that aid in avian seed dispersal. Capsaicinoids have many health benefits for humans: they are effective at inhibiting the growth of several forms of cancer [8][9][10] , are an analgesic for arthritis and other pain 11 , reduce appetite and promote weight loss [12][13][14] . It is surprising that a complete understanding of the capsaicinoid pathway at the molecular level is lacking, considering the economic and cultural importance of capsaicinoids.…”

Capsaicin may slow PSA doubling time: case report and literature review

“…It also results in a downregulation of AR and PSA expression in the presence of dihydrotestosterone, and increase in p53, p21 and Bax proteins which are involved in cell cycle regulation and apoptosis. 1 Capsaicin also has anti-proliferative activity in androgen-independent (AI) and AR negative cells and PC-3; it was found to induce apoptosis in 75% of the treated cells. 1 The mechanism for this activity likely involves multiple pathways involved in cell growth and stress-response.…”