Abstract
Background and Objective: Optimal clinical usefulness of Cisplatin is limited due to its nephro and neurotoxicity. The current study investigated whether dimethyl sulfoxide (DMSO) could enhance Cisplatin cytotoxic effects against the growth of A549 human lung carcinoma cell line. Materials and Methods: Cytotoxicity was determined using sulforhodamine-b (SRB) method,the changes of apoptosis induction using annexin V reagent, cell cycle phase distribution using flow cytometry. Moreover, Cisplatin cellular uptake was analyzed by Inductively Spectrometry (ICP-OES) and P glycoprotein activity by means of Rhodamine-123 dye assay. These parameters were measured in A549 lung cancer cells after treatment with Cisplatin and/or DMSO. Results: The DMSO treatment increased the cytotoxic activity of cisplatin manifested by a significant decrease in the IC50 (from 28.6 to 15.7 mu g mL(-1)). Cisplatin (5 or 20 mu g mL(-1)) and DMSO (10%) significantly decreased MDR activity with a significant increase in induction of apoptosis (81 and 84%) and accumulation of the cells in G0/G1 phase to 61.9 and 70.3%, respectively, compared to cisplatin treated cells. Conclusion: The DMSO treatment enhanced the cytotoxic activity of cisplatin against the growth of A549 cells by increasing Cisplatin cellular uptake, decreasing MDR function and disturbance of cell cycle.