Early apoptosis signals induced by a low dose of epigallocatechin 3-gallate interfere with apoptotic and cell death pathways

Abstract

Research for natural compounds with novel advantageous biological activities or antineoplastic potential is an important issue in drug discovery. An example of this type of compound is epigallocatechin 3-gallate (EGCG), which is the major polyphenol in green tea. EGCG has therapeutic effects and modulates multiple metabolic pathways, including apoptosis. The present study evaluates the effect of 10 microM EGCG on the expression of genes that are involved in apoptosis and cell death using PCR-array technology and HeLa cells as an in vitro model. The specific modulatory effects of EGCG were demonstrated by significant alterations in the expression levels of the following genes that control the apoptosis pathway: the TNF receptor and its ligand family, the death effector domain family, the Bcl-2 family or TP73. The structure of EGCG suggests that it has the potential to be an anticancer agent and that EGCG serves as a promising starting point for the derivation of novel anticancer drugs. EGCC metabolite products, such as pyrogallol, gallic acid or quinones, may also play important roles in inducing apoptosis. Therefore, quantification of mRNA using PCR-array technology is a valuable tool for screening these anticarcinogenic compounds. By evaluating the action of EGCG on genes that regulate apoptosis, our results suggest that EGCG is as an activator of gene expression with direct implications in cancer therapy. In addition, the limited success in activation of the antiapoptotic gene Bcl-2 may be associated with resistance to cancer treatment.