assay. These antagonists did not reverse the antiproliferative effect of capsaicin (data not shown), suggesting that the antiproliferative activity of capsaicin is distinct from its binding to TRPV1. We also studied the effect of the more potent vanilloid receptor agonist resiniferatoxin on LNCaP cells. Resin- iferatoxin was f10 times more potent in inhibiting proliferation compared with capsaicin. However, as was the case with capsaicin, the TRPV1 inhibitors ruthenium red and SB366791 were unable to affect the antiproliferative activity of capsaicin (data not shown).
Capsaicin inhibited human prostatic cancer xenografts. The effect of capsaicin on growth of human prostate cancer cells was studied in nude mice. PC-3 cells were injected into the flanks, and from the next day, capsaicin was given by gavage 3 days per week. Tumor volumes were measured weekly and all mice were killed at the end of the fourth week when tumors were dissected and weighted. Tumors in capsaicin-treated mice compared with those in vehicle-treated mice were statistically significantly smaller [75 F 35 versus 336 F 123 mm3 (FSD), respectively; P = 0.017]. Prostate tumors weighed significantly less in experimental versus diluent control mice [203 F 41 versus 373 F 52 mg, respectively
(P = 0.0006); Fig. 6A and B]. Mean body weights and hair coat as well as overall activity were similar in both groups at the completion of the experiment, suggesting that capsaicin had no major side effects on these mice (data not shown).
Recently, capsaicin has been receiving attention as an anticancer agent because of its pharmacologic and toxicologic properties (6–10). This study shows that capsaicin inhibits the growth of prostate cancer cells including androgen-independent PC-3 tumors growing in mice without causing gross toxicity of the animals. These results suggest that capsaicin may have a role for the management of prostate cancer patients, even for those who are refractory to hormonal therapy.
We explored the molecular mechanisms of capsaicin-induced growth inhibition and apoptosis in prostate cancer cells. A recent study suggested that expression of wild-type p53 is necessary for capsaicin-induced cellular growth inhibition and apoptosis of myeloid leukemia cells (NB4) via apoptosis (8). In our study, however, capsaicin inhibited growth and induced apoptosis not
Figure 3. Effects of capsaicin on dihydrotestosterone-induced PSA and AR levels and on transcriptional activity of the PSA promoter/enhancer in AR-overexpressing LNCaP cells. A, LNCaP cells were cultured (109 mol/L dihydrotestosterone, 24 hours) either with or without capsaicin (0.5, 1, or 2 104 mol/L). Western blot was sequentially probed for levels of PSA, AR, and GAPDH. B, LNCaP cells were cultured in the presence of dihydrotestosterone (109 mol/L, 24 or 48 hours) either with or without capsaicin (2 104 mol/L). AR mRNA levels were determined by real-time reverse transcription-PCR. Columns, ratio of AR transcripts/18S transcripts and means of three experiments; bars, FSD. C, LNCaP cells were transfected with PSA P/E-Luc and pCMV-AR, and cultured with dihydrotestosterone (108 mol/L) either with or without capsaicin (104 mol/L, 24 hours) and luciferase activity was determined. Columns, means of three or more experiments; bars, FSD. D, subcellular localization of AR analyzed by immunofluorescence. LNCaP cells were cultured for 12 hours in either dihydrotestosterone (1 107 mol/L; center), dihydrotestosterone and capsaicin (2 104 mol/L; right), or without the addition of drug (left).
Cancer Res 2006; 66: (6). March 15, 2006