Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line

Background and purpose: Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistance. The aim of this study was to determine the synergistic effect of combined clarithromycin and doxorubicin in lung cancer A549 cell line. Materials and methods: Combined cytotoxicity of doxorubicin and clarithromycin was evaluated by MTT assay in A549 cell line. The nature of the interaction observed between doxorubicin and clarithromycin was analyzed in Compusyn software based on Chou and Talalay method. In order to clarify the molecular mechanism of the drug synergism, apoptosis was measured by Annexin V/PI double staining. Results: Clarithromycin at 500 µM synergistically reduced the IC50 value of doxorubicin. The enhanced cytotoxicity of doxorubicin by clarithromycin was associated with increased apoptotic cell death in A549 cell line. Conclusion: Clarithromycin is a suitable candidate when combined with other anticancer drugs in vitro. However, more investigations are needed to evaluate the application of clarithromycin in adjuvant cancer therapy.