The effects of combination drug treatment with Caffeic Acid Phenethyl Ester (CAPE) and Zebularine (ZEB) on human lung cancer cell line A549

Abstract

lntroduction/Aim: Lung carcinoma is the leading cause of malignant tumor reİated mortality in the world. Caffeic acid phenethyl ester (CAPE) is a bioactive compound of propolis extract and possesses antimicrobial, antioxidant, anti-inflammatory, and cytotoxic properties. ZebuIarine (ı-(B-D- ribofuranosyl)-1,2-dihydropyrimidin-2-one) is an inhibitor of DNA methyltransferase (DNMT).The aim of this study is to explore the cytotoxic effects and cell proliferation of using single drug CAPE, ZEB and combination of these drugs on human lung cancer cell line ,4549. Materials and Methods: A549 celts were cultured in RPMl supplemented with ıo% fetal bovine serum (FBS) in a humidified atmosphere of 5% CO2 at 37 "C respectively. Cel| viability was determined by MTT assay that assesses the relative percentage of metabolically active cells compared to untreated cells. For MTT assay the dosage range of CAPE and ZEB and different dosage of two druş.The lC5o (concentration that inhibits 5o% of cell growth) was calculated for any drugs and combination with CAPE and ZEB. For ceII viability, cells were treated with IC5o value for each drug and combination z4h, 48h, 7zh, 96h of incubation. Results: We compared the effect of single drug treatment and combination drug treatment with CAPE and ZEB to control group for lung cancer cell line. MTT Assay's data showed that the lC5o of (APE 5o pıM, ZEB 5o p.M and combination therapy with CAPE zo pıM + ZEB 20 pM for z4h. According to the survival analysis showed that combination therapy with CAPE and ZEB for z4h, 48h, 7zh and 96h significantly reduced cell viability. ln addition, combination therapy indicated toxic effect after z4 hours on lung cancer cells, Conclusion: MTT and Survival assays for the evaluation of the effect of combination therapy on 4549 human lung cancer cells showed a decrease in cell viability. Combination therapy more effective than single therapy and using combination therapy decreases the cytotoxic effects of drugs. This study using CAPE and ZEB may an attractive candidate for tung cancer treatment for future.