الفهرس | Only 14 pages are availabe for public view |
Abstract The conventional chemotherapy remains one of the best choices for cancer treatment; however, treatment failures are common because of drug resistance and its side effects. Ethylenediamine tetra acetic acid (EDTA) is used in several biomedical applications. This study was conducted to evaluate the effect of co-treatment with EDTA on cisplatin (Cis) efficacy as anticancer agent in both of in vitro and in vivo studies. MCF-7 cells were treated either with different concentrations of Cis, EDTA, or with their combinations for 24h in vitro. The median inhibitory concentration (IC50) was determined by MTT assay. The percentages of apoptotic, necrotic, and cell cycle analysis of MCF-7 cells were assessed by flow cytometry. For in vivo study, different groups of EAC-bearing mice were treated either with different doses of Cis, different doses of EDTA, or with different combinations of Cis/EDTA. The % of b.wt change, total tumor volume, live, and dead tumor cells were assessed. Hematological, biochemical, and histological alterations were determined at the end of the experiment. The results showed that the co-treatment with EDTA enhanced the efficacy of the 1/10 of IC50 of Cis in vitro. Cis/EDTA cotreatment increased the % of apoptotic and necrotic MCF-7 cells after 24 h of treatment to 26.57 and 16.28%, respectively. Furthermore, this treatment arrested MCF-7 cell cycle at G0 phase (32.8%) and G2/M phase (30.25%). Co-treatment of EAC-bearing mice with EDTA (50 mg/Kg)/ Cis (0.5 mg/Kg) for 6 days showed the optimal condition to induce a maximum anticancer effect. This study clearly showed that the low concentrations or doses of EDTA were able to increase the anticancer fficacy of the low dose of Cis in both in vitro and in vivo studies. |