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

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 6; pp. 3222 - 3229
• Main Authors: MORI, Akio, LEHMANN, Sören, O'KELLY, James, KUMAGAI, Takashi, DESMOND, Julian C, PERVAN, Milena, MCBRIDE, William H, KIZAKI, Masahiro, KOEFFLER, H. Phillip
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.03.2006
• Subjects: Animals; Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Capsaicin - pharmacology; Cell Cycle - drug effects; Cell Growth Processes - drug effects; Down-Regulation - drug effects; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Mice; Mice, Nude; Mutation; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Nephrology. Urinary tract diseases; NF-kappa B - genetics; Pharmacology. Drug treatments; Promoter Regions, Genetic - drug effects; Prostate-Specific Antigen - biosynthesis; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptors, Androgen - biosynthesis; Receptors, Androgen - genetics; Transcription, Genetic - drug effects; Tumor Suppressor Protein p53 - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Xenograft Model Antitumor Assays; Urinary system disease; Prostate disease; Androgen; Capsaicin; Growth; Pepper; Malignant tumor; TP53 Gene; Hormonoindependence; Inhibitor; Mutation; Sex steroid hormone; Male genital diseases; Prostate cancer; Tumor cell; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-05-0087

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 suggests that capsaicin, or a related analogue, may have a role in the management of prostate cancer.