Antitumor Activity of Capsaicin on Human Colon Cancer Cells in Vitro and Colo 205 Tumor Xenografts in Vivo

Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei 112, Taiwan.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 11/2010; 58(24):12999-3005. DOI: 10.1021/jf103335w
Source: PubMed


Capsaicin was reported to inhibit cancer cell growth. The aim of this study was to evaluate the antitumor potential of capsaicin by studying antitumor activity in vitro as well as in vivo. The in vitro studies are to examine the effects of capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The results showed that capsaicin induced cytotoxic effects in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential (ΔΨ(m)) in colo 205 cells. Data from Western blotting analysis indicated that the levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In vivo studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed that capsaicin effectively inhibited tumor growth. The potent in vitro and in vivo antitumor activities of capsaicin suggest that capsaicin might be developed for the treatment of human colon cancer.

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    • "More recently, anticancer activity of capsaicin has been demonstrated [6]. Capsaicin-mediated apoptosis and/or antiproliferative potential has been reported for numerous cancer cell lines, e.g., in leukemia cells [7], multiple myeloma cells [8], cutaneous cell carcinoma [9], glioma cells [10], tongue cancer cells [11], nasopharyngeal carcinoma cells [12], esophageal carcinoma cells [13], gastric cancer cells [14], pancreatic cancer cells [15], hepatocarcinoma cells [16], colon carcinoma cells [17], small cell lung cancer [18], breast cancer cells [19] and prostate cancer cells [20]. It is widely accepted that capsaicin-associated anticancer effects may be executed by reactive oxygen species (ROS) production, cell cycle arrest, regulation of transcription factor expression and changes in growth/survival signal transduction pathways, such as EGFR/HER-2 pathway or NF-␬B inactivation [9,15,19,21–24]. "
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    ABSTRACT: Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥100μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Mutation Research/Genetic Toxicology and Environmental Mutagenesis
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    • "We suggest that ROS is an important cellular mediator that triggers the intrinsic- and mitochondrial-dependent apoptotic pathway through depletion of fatty acid synthesis after administration of capsaicin in HepG2 cells. Our suggestion is in agreement with other studies reporting that capsaicin coupled with the TRPV1 receptor and exerted apoptosis is mediated by an increase of ROS production in human cancer cells, such as nasopharyngeal carcinoma [13], colon cancer cells [53], and bladder cancer T24 cells [54]. Besides ROS-mediated apoptosis, several studies have reported that the effect of capsaicin to induce apoptosis is mediated by an increase of intracellular calcium following activation of the TRPV1 receptor in glioma cells [9] and human urothelial cancer (UC) cells [55]. "
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    ABSTRACT: The inhibition of the mammalian de novo synthesis of long-chain saturated fatty acids (LCFAs) by blocking the fatty acid synthase (FASN) enzyme activity in tumor cells that overexpress FASN can promote apoptosis, without apparent cytotoxic to non-tumor cells. The present study aimed to focus on the potent inhibitory effect of capsaicin on the fatty acid synthesis pathway inducing apoptosis of capsaicin in HepG2 cells. The use of capsaicin as a source for a new FASN inhibitor will provide new insight into its possible application as a selective anti-cancer therapy. The present findings showed that capsaicin promoted apoptosis as well as cell cycle arrest in the G0/G1 phase. The onset of apoptosis was correlated with a dissipation of mitochondrial membrane potential (ΔΨm). Apoptotic induction by capsaicin was mediated by inhibition of FASN protein expression which was accompanied by decreasing its activity on the de novo fatty acid synthesis. The expression of FASN was higher in HepG2 cells than in normal hepatocytes that were resistant to undergoing apoptosis following capsaicin administration. Moreover, the inhibitory effect of capsaicin on FASN expression and activity was found to be mediated by an increase of intracellular reactive oxygen species (ROS) generation. Treatment of HepG2 cells with capsaicin failed to alter ACC and ACLY protein expression, suggesting ACC and ACLY might not be the specific targets of capsaicin to induce apoptosis. An accumulation of malonyl-CoA level following FASN inhibition represented a major cause of mitochondrial-dependent apoptotic induction instead of deprivation of fatty acid per se. Here, we also obtained similar results with C75 that exhibited apoptosis induction by reducing the levels of fatty acid without any change in the abundance of FASN expression along with increasing ROS production. Collectively, our results provide novel evidence that capsaicin exhibits a potent anti-cancer property by targeting FASN protein in HepG2 cells.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "Ito et al demonstrated that capsaicin daily injection (50mg/kg) significantly inhibited leukemia cell in vivo growth without any organ damage observed 6. Zhang et al showed that injection of capsaicin (2.5mg/kg) 5 times a week was effective in reducing AsPC-1 human pancreatic xenograft growth in nude mice 43. Two investigations also showed that capsaicin at 3mg/kg or 10mg/kg could substantially attenuate the xenograft growth of human colon cancer Colo205 or HT29 respectively 44, 45. However, a study performed by Yang et al showed that capsaicin may promote colorectal cancer metastasis via modulating Akt/mTOR and STAT-3 pathways in vivo 46. "
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    ABSTRACT: Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.
    Preview · Article · Feb 2014 · International journal of biological sciences
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