ÇIĞIR BİRAY AVCI, Z ÖZLEM DOĞAN, SUNDE YILMAZ, SİNEM NUMANOĞLU, NEJAT TOPÇUOĞLU, CUMHUR GÜNDÜZ
Advances in Molecular Medicine - 2007;3(1):45-48
Objectives: Chemotherapeutic agents currently used for treatment of cancer have been derived from natural sources. Complications associated with classical drugs have brought new researches to develop new cancer treatment agents. CAPE (caffeic acid phenethyl ester) is one of the most effective components of propolis which is collected by honey bees. CAPE is in the structure of flavanoids and also active component of propolis. It has antiviral, anti-inflammatory, immunomodulatory and antiproliferative effects occur in different conditions. Anti-proliferative effect of CAPE has been considered as a new anti-cancer treatment modality and studied in many cell lines in vitro. Resveratrol is a natural polyphenol present in red wines and other constituents of the human diet. Resveratrol causes a complete and reversible cell cycle arrest in the S and G2 phases. Also it has been reported to inhibit cell growth and induce apoptosis in various solid and hematological cancer cell lines. The aim of the study is to determine the expression profiles of p53 (tumor antigen p53), which is a tumor suppressor gene, PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide), hTERT (human Telomerase Reverse Transcriptase) MDM2 (transformed 3T3 cell double minute 2), which are oncogenes in cancer. We used MCF-7 (human, Caucasian, breast, adenocarcinoma) as a model cell line. Methods: To investigate the role of gene expressions PIK3CA, MDM2, p53 and hTERT in resveratrol and CAPE induced apoptosis of breast carcinoma cells, we performed cytotoxicity, apoptosis and expression analysis, respectively. We determined IC50 values of resveratrol and CAPE in MCF-7 cells. IC50 doses of resveratrol (150µM) and CAPE (75µM) were treated merely and in combination for 72 hours. Gene expressions were examined in MCF-7 cells by reverse transcriptase polymerase chain reaction (RT-PCR). Results: MCF-7 cell line showed significant increase in p53, MDM2 and PIK3CA gene expression and reduction in hTERT expression when treated with IC50 doses of resveratrol and CAPE in 24th hour. Conclusion: In conclusion our study shows that anticarcinogenic properties of polyphenols such as resveratrol and CAPE are likely to be mediated by upregulation of p53 gene expression. Resveratrol and CAPE also induced apoptosis via p53 mediated pathway. Upregulated PIK3CA gene expression may be due to estrogen receptor-dependent mechanism in MCF-7 cells. Also down-regulation of hTERT, a gene which ensures immortality, is important for treatment schedule. This study provides support for the use of resveratrol and CAPE especially in combination in chemoprevention and cancer therapy trials
