Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation.
Many studies have focused on the anticarcinogenic, antimutagenic or chemopreventive activities 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 counterparts (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 dominant 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.
Kim
Seonhoe
S
College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea.
Moon
Aree
A
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001940:Breast / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D006131:Growth Inhibitors; D017382:Reactive Oxygen Species; D020744:rac GTP-Binding Proteins; D002211:Capsaicin