Browse > Article

Capsaicin-Induced Apoptosis of H-Ras-Transformed Human Breast Epithelial Cells is Rac-Dependent via ROS Generation  

Kim, Seon-Hoe (College of Pharmacy, Duksung Women＇s University)
Moon, Aree (College of Pharmacy, Duksung Women＇s University)
Publication Information
Archives of Pharmacal Research / v.27, no.8, 2004 , pp. 845-849 More about this Journal
Abstract
Many studies have focused on the anticarcinogenic, antimutagenic or chemopreventive activi-ties of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) which is a major pungent ingredient in red pepper. We have previously shown that capsaicin selectively induces apoptosis in H-ras-transformed MCF10A human breast epithelial cells but not in their normal cell counter-parts (Int. J. Cancer, 103, 475-482,2003). In this study, we investigated the possible roles of reactive oxygen species (ROS) and Rac1 in capsaicin-induced apoptosis of H-ras MCF10A cells. Selective induction of ROS generation by capsaicin treatment was observed only in H-ras MCF10A cells. Pretreatment of H-ras MCF10A cells with an antioxidant N-acetylcysteine(NAC) significantly reversed capsaicin-induced growth inhibition, suggesting that ROS may mediate the apoptosis of H-ras-transformed cells induced by capsaicin. Rac1 was prominently activated by H-ras in MCF10A cells. Based on the studies using a wild type Rac1 and a domi-nant negative Rac1 constructs, we propose that Rac1 activity is critical for inhibitory effect of capsaicin on growth of H-ras-transformed MCF10A cells possibly through ROS generation.
Keywords
Capsaicin; Reactive oxygen species(ROS); Rae; H-ras; MCF10A cells;
Citations & Related Records

Times Cited By Web Of Science : 16  (Related Records In Web of Science)
Times Cited By SCOPUS : 15
연도 인용수 순위
1 Takahata, K., Chen, X., Monobe, K., and Tada, M., Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular calcium mobilization. Life Sci., 64, PL165-171 (1999)   DOI   PUBMED   ScienceOn
2 Iwai, K., Suzuki, T., and Fujiwake, H., Formation and accumu-lation of pungent principle of hot pepper fruits, capsaicin and its analogues, in Capsicum annuum var.annuum cv. Karayatsubusa at different growth stages after flowering. Agric. Biol. Chem., 43, 2493-2498 (1979)   DOI
3 Macho, A., Calzado, M. A., Munoz-Blanco, J., Gomez-Diaz, C., Gajate, C., Mollinedo, F., Navas, P., and Munoz, E., Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ., 6, 155-165 (1999)   DOI   ScienceOn
4 Moon, A., Kim, M. S., Kim, T. G., Kim, S. H., Kim, H. E., Chen, Y. Q., and Kim, H. R., H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: a role for MMP-2 in the H-ras-induced invasive phenotype. Int. J. Cancer, 85, 176-181 (2000)
5 Bos, J. L., Ras oncogenes in human cancer: a review. Cancer Res., 49, 4682-4689 (1989)   PUBMED
6 Macho, A., Blazquez, M. V., Navas, P., and Munoz, E., Induction of apoptosis by vanilloid compounds does not require de novo gene transcription and activator protein 1 activity. Cell Growth Differ., 9, 277-286 (1998)
7 Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T., and Bokoch, G. M., Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science, 254, 1512-1515 (1991)   DOI   PUBMED
8 Kang, H. J., Soh, Y., Kim, M. S., Lee, E. J., Surh, Y. J., Kim, H. R., Kim, S. H., and Moon, A., Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells. Int. J. Cancer, 103, 475-482 (2003)   DOI   ScienceOn
9 Kim, M. S., Lee, E. J., Kim, H. R., and Moon, A., p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res., 63, 5454-5461 (2003)   PUBMED
10 Cordell, G. A. and Araujo, O. E., Capsaicin: identification, nomenclature, and pharmacotherapy. Ann. Pharmacother., 27, 330-336 (1993)   PUBMED
11 Sundaresan, M., Yu, Z. X., Ferrans, V. J., Sulciner, D. J., Gutkind, J. S., Irani, K., Goldschmidt-Clermont, P. J., and Finkel, T., Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Biochem. J., 318 (Pt 2), 379-382 (1996)
12 Jung, M. Y., Kang, H. J., and Moon, A., Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett., 165, 139-145 (2001)   DOI   ScienceOn
13 Bokoch, G. M., Regulation of cell function by Rho family GTPases. Immunol. Res., 21, 139-148 (2000).   DOI   ScienceOn
14 Soule, H. D., Maloney, T. M., Wolman, S. R., Peterson, W. D., Jr., Brenz, R., McGrath, C. M., Russo, J., Pauley, R. J., Jones, R. F., and Brooks, S. C., Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res., 50, 6075-6086 (1990)   PUBMED
15 Lee, Y. S., Kang, Y. S., Lee, J.,S., Nicolova, S., and Kim, J. A., Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Radic. Res., 38, 405-412 (2004)   DOI   ScienceOn
16 Benard, V., Bohl, B. P., and Bokoch, G. M., Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J. Biol. Chem., 274, 13198-13204 (1999)   DOI   ScienceOn
17 Surh, Y. J., Lee, E., and Lee, J. M., Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutat. Res., 402, 259-267 (1998)   DOI   PUBMED
18 Morre, D. J., Chueh, P. J., and Morre, D. M., Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture. Proc. Natl. Acad. Sci. U.S.A., 92, 1831-1835 (1995)   DOI   ScienceOn
19 Bokoch, G. M. and Diebold, B. A., Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood, 100, 2692-2696 (2002)   DOI   ScienceOn
20 Irani, K., Xia, Y., Zweier, J. L., Sollott, S. J., Der, C. J., Fearon, E. R., Sundaresan, M., Finkel, T., and Goldschmidt-Clermont, P. J., Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science, 275, 1649-1652 (1997)   DOI   PUBMED   ScienceOn
21 Wolvetang, E. J., Larm, J. A., Moutsoulas, P., and Lawen, A., Apoptosis induced by inhibitors of the plasma membrane NADH-oxidase involves Bcl-2 and calcineurin. Cell Growth Differ., 7, 1315-1325 (1996)
22 Suzuki, T. and Iwai, K., Constitution of red pepper species: chemistry, biochemistry, pharmacology, and food science of the pungent principle of capsicum species. In: Brosi A, ed. The alkaloides. New York: Academic Press, 227-299 (1984)
23 Kong, A. N., Yu, R., Chen, C., Mandlekar, S., and Primiano, T., Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Arch. Pharm. Res., 23, 1-16 (2000)   DOI   ScienceOn
24 Barbacid, M., Ras genes. Annu. Rev. Biochem., 56, 779-827 (1987)   DOI   PUBMED   ScienceOn
25 Denhardt, D. T., Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling. Biochem. J., 318 (Pt 3),729-747 (1996)
26 Lee, Y. S., Nam, D. H., and Kim, J. A., Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett., 161,121-130 (2000)   DOI   ScienceOn
27 Sander, E. E., van Delft, S., ten Klooster, J. P., Reid, T., van der Kammen, R. A., Michiels, F., and Collard, J. G., Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J. Cell Biol., 143, 1385-1398 (1998)   DOI   ScienceOn
28 Abo,A., Pick, E., Hall, A., Totty, N.,Teahan, C. G., and Segal, A. W., Activation of the NADPH oxidase involves the small GTP-binding protein p21 rac1. Nature, 353, 668-670 (1991)   DOI   ScienceOn
29 Schwieger, A., Bauer, L.; Hanusch, J., Sers, C., Schafer, R., and Bauer, G., Ras oncogene expression determines sensitivity for intercellular induction of apoptosis. Carcinogenesis, 22, 1385-1392 (2001)   DOI   ScienceOn
30 Jacobson, M. D., Reactive oxygen species and programmed cell death. Trends Biochem. Sci., 21, 83-86 (1996)   PUBMED