Direct Inhibition of Insulin-Like Growth Factor-I Receptor Kinase Activity by (−)−Epigallocatechin-3-Gallate Regulates Cell Transformation

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 16; no. 3; pp. 598 - 605
• Main Authors: MING LI, ZHIWEI HE, BODE, Ann M, YA CAO, ZIGANG DONG, ERMAKOVA, Svetlana, DUO ZHENG, FAQING TANG, CHO, Yong-Yeon, FENG ZHU, MA, Wei-Ya, SHAM, Yuk, ROGOZIN, Evgeny A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.2007
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Antineoplastic agents; Biological and medical sciences; Blotting, Western; carcinogenesis; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Transformation, Neoplastic - drug effects; Chemotherapy; EGCG; IGF-IR; kinase; Medical sciences; Mice; Mice, Nude; Pharmacology. Drug treatments; Phenotype; Receptor, IGF Type 1 - antagonists & inhibitors; signal pathway; Signal Transduction; Antineoplastic agent; Human; Chemoprophylaxis; Enzyme; Transferases; Enzyme inhibitor; Breast cancer; Malignant tumor; Anticarcinogen; Insulin like growth factor 1; Cell transformation; Female genital diseases; Prevention; Mammary gland diseases; Epigallocatechin gallate; Cancerology; Protein-tyrosine kinase; Uterine cervix diseases; Cervical cancer; Biological receptor
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-06-0892

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 (IC 50 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)