Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells.
Although capsaicin (8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient in a variety of red peppers of the genus Capsicum, has been shown to induce apoptotic cell death in many cancer cells, the exact mechanism of this action of capsaicin is not completely understood. In this study, we investigated the possible mediation of the NADPH oxidase-modulated production of reactive oxygen species (ROS) in the apoptotic mechanism of capsaicin in HepG2 human hepatoblastoma cells. Capsaicin induced apoptotic cell death in a time- and dose-dependent manner. Capsaicin at the concentration of inducing apoptosis also markedly increased the level of ROS. The capsaicin-induced generation of ROS and apoptosis was significantly suppressed by treatment with antioxidants, DPPD and tocopherol. In addition, inhibitors of NADPH oxidase, diphenylene iodonium, apocynin and neopterine, profoundly blocked the capsaicin-induced ROS generation and apoptosis. The expression of Rac1N17, a dominant negative mutant of Rac1, also significantly inhibited the capsaicin-induced apoptosis. Activation of nuclear factor-kappaB, a transcription factor essentially involved in ROS-induced apoptosis, was also observed by treatment with capsaicin. Collectively, these results suggest that the NADPH oxidase-mediated generation of ROS may be essentially involved in the mechanism of capsaicin-induced apoptosis in HepG2 cells. These results further suggest that capsaicin may be a valuable agent for the therapeutic intervention of human hepatomas.
Lee
Yong Soo
YS
College of Pharmacy, Duksung Women's University, Seoul 132-714, South Korea.
Kang
Young Shin
YS
Lee
Ji-Seon
JS
Nicolova
Sevdalina
S
Kim
Jung-Ae
JA
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005799:Genes, Dominant; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D019255:NADPH Oxidases / Q000737:chemistry* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species; D013997:Time Factors; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D004247:DNA; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein; D002211:Capsaicin