Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin |
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Authors: | A. M. Sánchez M. G. Sánchez S. Malagarie-Cazenave N. Olea I. Díaz-Laviada |
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Affiliation: | (1) Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid, 28871, Spain;(2) Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, 28871, Spain |
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Abstract: | Capsaicin, the pungent ingredient of hot chilli pepper, has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. Here, we investigated the role of the vanilloid capsaicin in the death regulation of the human cancer androgen-resistant cell line PC-3. Capsaicin inhibited the growth of PC-3 with an IC50 of 20 μM cells and induced cell apoptosis, as assessed by flow cytometry and nuclei staining with DAPI. Capsaicin induced apoptosis in prostate cells by a mechanism involving reactive oxygen species generation, dissipation of the mitochondrial inner transmembrane potential (ΔΨm) and activation of caspase 3. Capsaicin-induced apoptosis was not reduced by the antagonist capsazepine in a dose range from 0.1 μM to 20 μM, suggesting a receptor-independent mechanism. To study the in vivo effects of capsaicinoids, PC-3 cells were grown as xenografts in nude mice. Subcutaneous injection of either capsaicin or capsazepine (5 mg/kg body weight) in nude mice suppressed PC-3 tumor growth in all tumors investigated and induced apoptosis of tumor cells. Our data show a role for capsaicin against androgen-independent prostate cancer cells in vitro and in vivo and suggest that capsaicin is a promising anti-tumor agent in hormone-refractory prostate cancer, which shows resistance to many chemotherapeutic agents. |
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Keywords: | capsaicin capsazepine PC-3 cells prostate cancer vanilloids xenograft tumor |
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