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Chemopreventive effects of curcumin on chemically induced mouse skin carcinogenesis in BK5.insulin-like growth factor-1 transgenic mice

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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.

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Acknowledgment

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST) (331-2008-1-C00308).

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Authors and Affiliations

  1. Department of Food Science and Nutrition, Catholic University of Daegu, 13-13 Hayangro, Hayangeup, Gyeongsan, Gyeongbuk, 712-702, South Korea

    Hyoseon Kim, Jeongeun Park, Ka-Hee Tak & Eunjung Kim

  2. Department of Food and Nutrition, Daegu University, 201 Daegudaero, Jillyangeup, Gyeongsan, Gyeongbuk, 712-714, South Korea

    So Young Bu

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  1. Hyoseon Kim
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  2. Jeongeun Park
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  3. Ka-Hee Tak
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  5. Eunjung Kim
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Correspondence to Eunjung Kim.

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Editor: T. Okamoto

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Kim, H., Park, J., Tak, KH. et al. Chemopreventive effects of curcumin on chemically induced mouse skin carcinogenesis in BK5.insulin-like growth factor-1 transgenic mice. In Vitro Cell.Dev.Biol.-Animal 50, 883–892 (2014). https://doi.org/10.1007/s11626-014-9791-9

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  • DOI: https://doi.org/10.1007/s11626-014-9791-9

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