title: Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor (IGF)-1 signaling in mouse skin cancer.
abstract: It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.
authors.affiliation: Department of Food Science and Nutrition, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Food and Nutrition, Daegu University, Gyeongbuk 712-714, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Bu
authors.affiliation: Department of Food Science and Nutrition, Catholic University of Daegu, 13-13 Hayangro, Hayangeup, Gyeongsan, Gyeongbuk 712-702, Korea.
authors.forename: Ka-Hee
authors.initials: KH
authors.lastname: Tak
authors.affiliation: Department of Food Science and Nutrition, Catholic University of Daegu, 13-13 Hayangro, Hayangeup, Gyeongsan, Gyeongbuk 712-702, Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Food Science and Nutrition, Catholic University of Daegu, 13-13 Hayangro, Hayangeup, Gyeongsan, Gyeongbuk 712-702, Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
keywords: IGF-1; Quercetin; carcinogenesis; mouse skin cancer