Investigation of Cytotoxic and Anti proliferative effects of Doxorubucin DOX and Caffeic Acid Phenetyl Ester CAPE on MDA MB 231 breast cancer cell line

Abstract

For some cancers, chemotherapy drugs are most effective when given in combirıation. Because single-agent treatrnent often results in cytotoxic effect due to the high dose.The purpose for cornbination chemotherapy is to use that work by different mechanisms, therefore reducing the possibility that cytotoxic effect will develop. Doxorubucin acts in the cancer cell intercalation into DNA and corruption of topoisomerase-II mediated DNA repair and generation of free radicals and their damage to cellular membranes, DNA and proteins. Anti-metabolite drugs function by inhibiting basic biosynthetic processes, or by being included into macromolecules, such as DNA and RNA, and inhibiting their normal function. 5-fluorouracil(5-FU) does one of them. In a study, it showed thatresults of combining chemotherapeutic drugs, such as 5-FU with propranolol at the lowest effective concentration in synergistic or antagonistic effects on cell proliferation in vitro depending on cell type and used chemotherapy. Furthermore, in this study, we aimed to decrease the cytotoxic effects of these drugs in a single treatment. So we treated triple combination of these drugs in literature for the first time. MCF-7 breast cancer ceil line was cuitured and maintained in RPM| mediıım inciuding with 10%(v/v) fetal calf serum and 1% (v/v) penicillin/streptomycin, at 37C in a humidified atmosphere contaning 5% carborı dioxide- MTT assay was performed to evaluate the effects of different concentrations of Doxorubucin, 5-Fluorouracil, Propranolol and triple cornbination of these drıugs for 24 h- To deterrnine the cytotoxic effect of drugs combination was used in survival assay. After the incubation, cells were treated with doxorubich and 48h. We observed that IC50 values 0.01 mg/ml for doxorubucin, 3 mg/ml for 5-FU, 30 mg/ml for propranolol and 0.2/1/30 mg/ml for respectively doxorubucin, 5-FU and propranolol combination by MTT assay. We detected that cytotoxic effect of these drugs with triple treatment are less than single treatment on growth assay. The recent studies revealed that triple combination therapy was a potential candidate for chemotherapy. In this study triple combination of doxorubucin, 5-FU and propranolol are treated for first time in literature. Thus cytotoxic effect of these drugs with triple treatment can be reduced more than single treatment. In future, understanding the mechanism of these drugs of combination will assist the clinic studies.