Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin

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 IC(50) of 20 microM 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 (DeltaPsi(m)) and activation of caspase 3. Capsaicin-induced apoptosis was not reduced by the antagonist capsazepine in a dose range from 0.1 microM to 20 microM, 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.

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

“…The absence of TRPV1 in the P2 pancreas suggests that neonatal capsaicin could not affect pancreatic cells via a receptor-specific mechanism. However, as noted by Diaz-Laviada and Rodriguez-Henche (41), for many tumor cell lines, capsaicin effects, especially with respect to alterations in apoptosis or proliferation, are TRPV1 independent (33,42,43). We therefore examined pancreata from P2 vehicle-and capsaicintreated mice stained for markers of apoptosis (anticaspase 3) and proliferation (anti-Ki67) 2 h posttreatment.…”

“…To examine how sensory neurons impact PDAC initiation and progression, we first determined if neonatal capsaicin had direct effects on pancreatic cells because previous studies using cancer-derived cell lines showed it affected apoptosis and proliferation (28)(29)(30)(31)(32)(33)(34). The neurotoxic effects of neonatal capsaicin treatment are assumed to be via binding to TRPV1, the vanilloid receptor specific for capsaicin.…”

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

“…The association between capsaicin and carcinogenesis has long been investigated, which, however, reached paradoxical observations in different tumor types. It is reported that capsaicin displayed an anti-proliferative activity against lung cancer [5], prostate cancer [6] and pancreatic cancer [7]; nevertheless, capsaicin also acts as a co-carcinogen in the development of skin cancer [8]. Further, it is reported that capsaicin induced apoptosis in human breast cancer cell line through caspase-independent pathway [9].…”

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

“…1 Tumour growth of the PC-3 cells was reduced by 40% when capsaicin was administered to mice 4 weeks after tumour inoculation. 2 We report PSA stabilization on capsaicin in a patient with PSA relapse after radiotherapy for a T2b, Gleason score 7 adenocarcinoma of the prostate. At biochemical failure, the patient did not tolerate androgen ablation therapy and started taking habanero sauce containing capsaicin 2.5 to 5 mL daily in April 2006.…”

“…1 Capsaicin was also shown to induce apoptosis via reactive oxygen species (ROS) formation, dissipation of mitochondrial inner transmembrane potential and caspase 3 activation in PC-3 cells. 2 Further studies have shown that ROS generation may be necessary for ceramide accumulation and cell growth inhibition by capsaicin. 3 Pathways involving Jun N-terminal Kinase (JNK) and extracellular signal-regulated kinase (ERK) cascades have also been implicated in anti-proliferative effects of capsaicin.…”