Direct Inhibition of Insulin-Like Growth Factor-I Receptor Kinase Activity by (−)−Epigallocatechin-3-Gallate Regulates Cell Transformation
- Ming Li1,
- Zhiwei He1,
- Svetlana Ermakova1,
- Duo Zheng1,
- Faqing Tang1,
- Yong-Yeon Cho1,
- Feng Zhu1,
- Wei-Ya Ma1,
- Yuk Sham2,
- Evgeny A. Rogozin1,
- Ann M. Bode1,
- Ya Cao3 and
- Zigang Dong1
- 1Hormel Institute, University of Minnesota, Austin, Minnesota; 2Computational Biology/Biochemistry Consultant, Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota; and 3Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Requests for reprints:
Zigang Dong, Hormel Institute, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912. Phone: 507-437-9600; Fax: 507-437-9606. E-mail: zgdong{at}hi.umn.edu
Abstract
Insulin-like growth factor-I receptor (IGF-IR) has been implicated in cancer pathophysiology. Furthermore, impairment of IGF-IR signaling in various cancer cell lines caused inhibition of the transformed phenotype as determined by the inhibition of colony formation in soft agar and the inhibition of tumor formation in athymic nude mice. Thus, the IGF-IR might be an attractive target for cancer prevention. We showed that the tea polyphenol, (−)−epigallocatechin-3-gallate (EGCG), is a small-molecule inhibitor of IGF-IR activity (IC50 of 14 μmol/L). EGCG abrogated anchorage-independent growth induced by IGF-IR overexpression and also prevented human breast and cervical cancer cell phenotype expression through inhibition of IGF-IR downstream signaling. Our findings are the first to show that the IGF-IR is a novel binding protein of EGCG and thus may help explain the chemopreventive effect of EGCG on cancer development. (Cancer Epidemiol Biomarkers Prev 2007;16(3):598–605)
Footnotes
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Grant support: The Hormel Foundation and NIH grants CA81064 and CA88961.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: The University of Minnesota is an equal opportunity educator and an employer.
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- Accepted December 15, 2006.
- Received October 23, 2006.
- Revision received December 6, 2006.
