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Am J Physiol Cell Physiol 288: C1094-C1108, 2005. First published January 12, 2005; doi:10.1152/ajpcell.00569.2004
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GROWTH, DIFFERENTIATION, AND APOPTOSIS

Antimitogenic effect of green tea (–)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways

Pei-Fang Hung, Bo-Tsung Wu,* Hui-Chian Chen,* Yen-Hang Chen, Chia-Lin Chen, Ming-Hua Wu, Hsien-Chun Liu, Meng-Jung Lee, and Yung-Hsi Kao

Department of Life Science, College of Science, National Central University, Chung-Li City, Taoyuan, Taiwan

Submitted 23 November 2004 ; accepted in final form 5 January 2005

Green tea catechins, especially (–)-epigallocatechin gallate (EGCG), have been proposed as a chemopreventative for obesity, diabetes, cancer, and cardiovascular diseases. However, relatively little is known about the mechanism of the action of EGCG on fat cell function. This study was designed to investigate the pathways of EGCG's modulation of the mitogenesis of 3T3-L1 preadipocytes. Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU) was inhibited by EGCG in dose-, time-, and growth phase-dependent manners. Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D1 proteins, reduced Cdk2 activity, and increased levels of G0/G1 growth arrest, p21waf/cip, and p27kip1, but not p18ink, proteins and their associations to Cdk2. However, neither MEK1, ERK1/2, p38 MAPK, phospho-p38, JNK, nor phospho-JNK was changed. Increased phospho-ERK1/2 content and Cdk2 activity, respectively, via the transfection of MEK1 and Cdk2 cDNA into preadipocytes prevented EGCG from reducing cell numbers. These data demonstrate the ERK- and Cdk2-dependent antimitogenic effects of EGCG. Moreover, EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in changing the mitogenic signals. The signal of EGCG in reducing growth of 3T3-L1 preadipocytes differed from that of 3T3 fibroblasts. Results of this study may relate to the mechanism by which EGCG modulates body weight.

3T3-L1 preadipocyte; mitogen-activated protein kinase; cyclin-dependent kinase


Address for reprint requests and other correspondence: Y.-H. Kao, Dept. of Life Science, College of Science, National Central Univ., Chung-Li City, Taoyuan, Taiwan 32054 (E-mail: ykao{at}cc.ncu.edu.tw)




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