Browse > Article
http://dx.doi.org/10.3345/kjp.2008.51.3.307

Capsaicin induced apoptosis and the enhanced anticancer effect of anticancer drugs in cancer cells  

Kim, Sun Young (Research Institute of Clinical Medicine, Chonbuk National University)
Lee, You Jin (Research Institute of Clinical Medicine, Chonbuk National University)
Park, Eun Hye (Research Institute of Clinical Medicine, Chonbuk National University)
Yi, Ho Keun (Department of Biochemistry, School of Dentistry, Chonbuk National University)
Jo, Dae Sun (Department of Pediatrics, School of Medicine, Chonbuk National University)
Kim, Jung Soo (Department of Pediatrics, School of Medicine, Chonbuk National University)
Hwang, Pyoung Han (Department of Pediatrics, School of Medicine, Chonbuk National University)
Publication Information
Clinical and Experimental Pediatrics / v.51, no.3, 2008 , pp. 307-314 More about this Journal
Abstract
Purpose : Capsaicin, the major pungent ingredient in red pepper, has long been used in spices and food additives. It has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. The aim of this study was to investigate the apoptosis-inducing effect of capsaicin on gastric cancer cells, and to provide valuable information concerning the application of capsaicin for therapeutic purposes. Methods : Cultured SNU-668 cells were treated with capsaicin. We analyzed cell survival by trypan blue and crystal violet analysis, cell cytotoxicity by MTT assay, apoptosis by nuclear condensation and DNA fragmentation, bcl-2 and bax mRNA expression by RT-PCR, and the expression of apoptosis related proteins by Western immunoblot analysis. In order to assess whether the growth inhibitory effect of anticancer drugs is enhanced by capsaicin, we investigated the effects of cell cytotoxicity and the expression of apoptosis related proteins of etoposide and adriamycin treated with capsaicin in cells. Results : Capsaicin inhibited growth of SNU-668 cells in a dose-dependent manner. This inhibitory effect of capsaicin on cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation, nuclear condensation and the expression of apoptosis related proteins. Furthermore, capsaicin prominently reduced the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax and consequently increased caspase-3 activity. The cells treated with capsaicin were more sensitive to death induced by etoposide and adriamycin than the cells without capsaicin. Conclusion : These results demonstrate that capsaicin efficiently induced apoptosis in SNU-668 cells through a caspase-3-dependent mechanism and sensitizes cancer cells to anticancer drugs toward apoptotic cell death, which may contribute to its anticancer effect and chemosensitizer function against gastric cancer.
Keywords
Capsaicin; Apoptosis; Chemosensitivity; Gastric cancer;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Kato S, Aihara E, Nakamura A, Xin H, Matsui H, Kohama K, et al. Expression of vanilloid receptors in rat gastric epithelial cells: role in cellular protection. Biochem Pharmacol 2003;66:1115-21   DOI   ScienceOn
2 Anti M, Armuzzi A, Gasbarrini G. Epithelial cell turnover and apoptosis. Ital J Gastroenterol Hepatol 1998;Suppl 3:S276-8
3 Szallasi A, Blumberg PM. Vanilloid(Capsaicin) receptors and mechanism. Pharmacol Rev 1999:51:159-212
4 Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol 1996;34:313-6   DOI   ScienceOn
5 Kim JD, Kim JM, Pyo JO, Kim SY, Kim BS, Yu R, et al. Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1. Cancer Lett 1997;20:235-41   DOI   ScienceOn
6 Mori A, Lehmann S, O'Kelly J, Kumagai T, Desmond JC, Pervan M, et al. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 2006;66:3222-9   DOI   ScienceOn
7 Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N, Diaz-Laviada I. Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 2006;11:89-99   DOI
8 Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by bcl-2: release of cytochrome c from mitochondria blocked. Science 1997;275:1129-32   DOI   ScienceOn
9 Kobayashi T, Ruan S, Clodi K, Kliche KO, Shiku H, Andreeff M, et al. Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents. Oncogene 1998;16:1587-91   DOI
10 Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995;27:293-9
11 Steller H. Mechanisms and genes of cellular suicide. Science 1995;267:1445-9   DOI   ScienceOn
12 Surh YJ, Ahn SH, Kim KC, Park JB, Sohn YW, Lee SS. Metabolism of capsaicinoids: Evidence for alipathic hydroxylation and its pharmacological implications. Life sci 1995:56:305-11   DOI   ScienceOn
13 Lawson T, Gannett P. The mutagenicity of capsaicin and dihydrocapsaicin in V79 cells. Cancer Lett 1989;49:109-13
14 Lo YC, Yang YC, Wu IC, Kuo FC, Liu CM, Wang HW, et al. Capsaicin-induced cell death in a human gastric adenocarcinoma cell line. World J Gastroenterol 2005;11:6254-7   DOI
15 Key TJ, Allen NE, Spencer EA, Travis RC. The effect of diet on risk of cancer. Lancet 2002;360:861-8   DOI   ScienceOn
16 Mountz JD, Zhou T, Wu J, Wang W, Su X, Chen J. Regulation of apoptosis in immune cells. J Clin Immunol 1995;15:1-16   DOI
17 Kondo S, Yin D, Takeuchi J, Morimura T, Oda Y, Kikuchi H. Bcl-2 gene enables rescue from in vitro myelosuppression induced by chemotherapy. Br J Cancer 1994;70:421-6   DOI   ScienceOn
18 Alnemri ES. Mammalian cell death proteascs: a family of highly conserved aspartate specific cysteine proteases. J Cell Biochem 1997;64:33-42   DOI   ScienceOn
19 Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for bcl-2 regulation of apoptosis. Science 1997;275:1132-6   DOI   ScienceOn
20 Hong SP, Ha SH, Park IS, Kim WHo Induction of apoptosis in colon cancer cells by nonsteroidal anti-inflammatory drugs. Yonsei Med J 1998;39:287-95   DOI
21 Aggarwal BB, Takada Y, Oommen OV. From chemoprevention to chemotherapy: common targets and common goals. Expert Opin Investig Drugs 2004;13:1327-38   DOI   ScienceOn
22 Kim YS, Park HA, Kim BS, Yook JH, Lee MS. Efficacy of screening for gastric cancer in a Korean adult population: a case-control study. J Korean Med Sci 2000;15:510-5   DOI
23 Wolvetang EJ, Larm JA, Moutsoulas P, Lawen A. Apoptosis induced by inhibitors of the plasma membrane NADH-oxidase involves Bcl-2 and calcineurin. Cell Growth Differ 1996;7:1315-25
24 Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74:609-19   DOI   ScienceOn
25 Hockenbery D. Definding apoptosis. Am J Pathol 1995;146:16-9
26 Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994;73:2013-26   DOI   ScienceOn
27 Lee JS, Chang JS, Lee JY, Kim JA. Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. Arch Pharm Res 2004;27:1147-53   DOI   ScienceOn
28 Singh S, Natarajan K, Aggarwal BE. Capsaicin is a potent inhibitor of nuclear transcription factor-kappa B activation by diverse agents. J Immunol 1996;157:4412-20
29 Yin XM, Oltvai Z, Korsmeyer SJ. BH1 and BH2 domains of bcl-2 are required for inhibition of apoptosis and heterodimerization with bax. Nature 1994;369:321-3   DOI   ScienceOn
30 Macho A, Blazquez MV, Navas P, Munoz E, Induction of apoptosis by vanilloid compounds does not require de novo gene transcription and activator protein 1 activity. Cell Growth Differ 1998;9:277-86