title: Chemopreventive effects of curcumin on chemically induced mouse skin carcinogenesis in BK5.insulin-like growth factor-1 transgenic mice.
abstract: The insulin-like growth factor-1 (IGF-1) signaling pathway is strongly associated with the risk of various cancers, and its inhibition has emerged as a potent anticancer strategy. Accumulating evidence from in vitro studies has shown that curcumin is a potent inhibitor of the IGF-1 signaling pathway. However, direct evidence that curcumin modulates IGF-1-induced tumorigenesis in a physiological system has not been reported. Therefore, in this study, we assessed the anticarcinogenic activity of curcumin on skin cancer by using BK5.IGF-1 transgenic (Tg) mice that overexpress IGF-1 in the skin epidermis. In 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two-stage skin carcinogenesis, a curcumin diet (0.02% wt/wt) fed for 14 wk remarkably reduced mouse skin tumor multiplicity by 53%, epidermal hyperplasia and proliferation compared to the control diet group. TPA-induced phosphorylation of Akt, S6 kinase (S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) in mouse skin was lower in the curcumin group than in the control group. Curcumin treatment inhibited IGF-1-induced phosphorylation of the IGF-1 receptor, insulin receptor substrate-1, Akt, S6K, and 4EBP1 in the mouse keratinocyte cell line, C50 in a dose-dependent manner. Taken together, these data suggest that curcumin exerts significant anticarcinogenic activity in skin cancer through the inhibition of IGF-1 signaling.
authors.affiliation: Department of Food Science and Nutrition, Catholic University of Daegu, 13-13 Hayangro, Hayangeup, Gyeongsan, Gyeongbuk, 712-702, South Korea.
authors.forename: Hyoseon
authors.initials: H
authors.lastname: Kim
authors.forename: Jeongeun
authors.initials: J
authors.lastname: Park
authors.forename: Ka-Hee
authors.initials: KH
authors.lastname: Tak
authors.forename: So Young
authors.initials: SY
authors.lastname: Bu
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D003474:Curcumin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D003474:Curcumin