Investigation of caffeic acid phenethyl ester (CAPE) and DNA methyl transferase inhibitors (DNMTi) combination induced epigenetic modification in apoptotic mechanisms on MDA-MB-231 breast cancer cell line

Breast cancer is the most common cause of cancer deaths among women in the world and makes up approximately 30% all other cancer types among women. It is well known that some of the drugs' mechanisms of action, which are used in cancer therapy, triggers apoptotic cell death. Caffeic acid phenethyl ester (CAPE) which is important in biological activities, such as anti-bacterial, anti-viral, antioxidant, anti-inflamatory and anti-cancer, is known as a stimulant of apoptosis. In the previous studies, it is seen that with the activation of caspase-3 CAPE mediated apoptosis causes decrease in gene expression of BCL-2 and causes increase in general expression of Bax which is an antiapoptetic protein in human leukemia HL-60 cell lines. DNA methyl transferase inhibitors (DNMTi) are commonly used for inhibiting tumor cell death in clinical studies. Zebularine (ZEB) is a cytidine analog which includes 2-(1H)-pyrimidonone ring and is developed as a cytidine deaminase inhibitor to inhibit deamination of nucleoside analogs. Because of it low toxicity, it enables zebularine to be used alone or it is combined with other DNMT inhibitors in the long term and this situation may enable epigenetically silenced genes to be reactive in a high level again in cancer cells. In the study, it was aimed primarily to determine the effect of using CAPE and ZEB together on cell viability on MDA-MB-231 breast cancer cell line and later to determine the inductive effect on the apoptotic pathway. With the determination and examiation of the epigenetic changes in the proteins like caspase-7, caspase-9 and caspase-3 which are related with apoptotic pathway, it was aimed to determine the relation between apoptotic and epigenetic mechanisms. Keywords Breast cancer; Apoptosis; Epigenetic changes; Caffeic acid phenethyl ester (CAPE); DNA methyltransferase inhibitors (DNMTi)