Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts Zong Ping Chen a , John B. Schell a , Chi-Tang Ho b , Kuang Yu Chen a, * a Department of Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08855-0939, USA b Center for Advanced Food Technology, Rutgers, The State University of New Jersey, Piscataway, NJ 08855-0939, USA Received 5 February 1998; received in revised form 24 March 1998; accepted 24 March 1998 Abstract (-)-Epigallocatechin gallate (EGCG), a catechin polyphenol compound, represents the main ingredient of green tea extract. Although EGCG has been shown to be growth inhibitory in a number of tumor cell lines, it is not clear whether the effect is cancer-specific. In this study we compared the effect of EGCG on the growth of SV40 virally transformed WI38 human fibroblasts (WI38VA) with that of normal WI38 cells. The IC 50 value of EGCG was estimated to be 120 and 10 mM for WI38 and WI38VA cells, respectively. Thus, EGCG at 40 mM completely inhibited the growth of WI38VA cells, but had little or no inhibitory effect on the growth of WI38 cells. Similar differential growth inhibition was also observed between a human colorectal cancer cell line (Caco-2), a breast cancer cell line (Hs578T) and their respective normal counterparts. EGCG at a concentration range of 40–200 mM induced a significant amount of apoptosis in WI38VA cultures, but not in WI38 cultures, as determined by terminal deoxynucleotidyl transferase assay. After exposure to EGCG at 200 mM for 8 h, more than 50% of WI38VA cells in a confluent culture became apoptotic. In contrast, less than 1% of WI38 cells displayed apoptotic labeling under the same condition. EGCG did not affect the serum-induced expression of c-fos and c-myc genes in normal WI38 cells. However, it significantly enhanced their expression in transformed WI38VA cells. It is possible that differential modulation of certain genes, such as c-fos and c-myc, may cause differential effects of EGCG on the growth and death of cancer cells.  1998 Published by Elsevier Science Ireland Ltd. All rights reserved Keywords: EGCG; Cell proliferation; Apoptosis; Gene expression; c-Fos 1. Introduction Epidemiological studies, though inconclusive, sug- gest a protective effect of tea consumption on certain human cancers [1,2]. Animal studies show that green tea polyphenols inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents and inhibit TPA-induced skin tumor promotion in mice [3–6]. The green tea poly- phenols have also been shown to inhibit the prolifera- tion of cultured mammalian cells, including colon carcinoma, lung carcinoma, breast carcinoma, mela- noma and leukemic cells [7–10]. Six polyphenol com- pounds, (+ )-gallocatechin (GC), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate Cancer Letters 129 (1998) 173–179 0304-3835/98/$19.00  1998 Published by Elsevier Science Ireland Ltd. All rights reserved PII S0304-3835(98)00108-6 * Corresponding author. Department of Chemistry, Rutgers Uni- versity, P.O. Box 939, Piscataway, NJ 08855-0939, USA. Tel.: +1 732 4453739; fax: +1 732 4455312; e-mail: KYCHEN@rutchem.rutgers.edu