title: Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells.
abstract: Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras-transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis.
authors.affiliation: College of Pharmacy, Duksung Women's University, 4129 Ssangmun-dong, Tobong-ku, Seoul 132-714, Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Yunjo
authors.initials: Y
authors.lastname: Soh
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
authors.forename: Hyeong-Reh Choi
authors.initials: HR
authors.lastname: Kim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001940:Breast / Q000473:pathology*; D002211:Capsaicin / Q000378:metabolism*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010641:Phenotype; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C096429:L 709049; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002211:Capsaicin