Combining the chemotherapeutic effects of epigallocatechin 3-gallate with siRNA-mediated p53 knock-down results in synergic pro-apoptotic effects

Abstract

Ioana Berindan-Neagoe,1,2 Cornelia Braicu,1 Alexandru Irimie3,41Department of Functional Genomics and Experimental Pathology, Cancer Institute, “Ion Chiricuta”, Cluj-Napoca, Romania; 2Department of Immunology, University of Medicine and Pharmacy, “I. Hatieganu”, Cluj-Napoca, Romania; 3Department of Surgical Oncology, University of Medicine and Pharmacy, “I. Hatieganu”, Cluj-Napoca, Romania; 4Department of Surgery, Cancer Institute, “Ion Chiricuta”, Cluj-Napoca, RomaniaAbstract: Plant extracts and compounds are applied to a wide variety of diseases in which traditional drugs have proven ineffective. A quickly developing trend in biomedicine is the therapeutic use of siRNA (short interfering RNA) structures. The focus of this study was on evaluating the gene expression involved in the modulation of apoptosis, in cases of combinatorial treatment (-)-epigallocatechin-3-gallate (EGCG) and/or p53siRNA. EGCG in combination with p53siRNA exerts synergic pro-apoptotic effects that are greater than those of each agent taken individually. There is a cumulative antiproliferative effect, induced by EGCG and p53siRNA treatment, and it is mediated through the activation of a large number of pro-apoptotic genes and the inhibition of anti-apoptotic protein expression levels. p53siRNA promotes the convergence of the extrinsic and intrinsic pathways in a synergic manner with EGCG. The chemotherapeutic effects of EGCG in combination with p53siRNA therapy induced a synergic pro-apoptotic effect, indicating the potential for development of promising new anticancer therapies.Keywords: p53siRNA, apoptosis, HeLa cells