the sensitization of melatonin in osteosarcoma cells by suppression of anti-apoptotic proteins

Background: investigation of anti-cancer agents with desirable selective toxicity is critical for cancer therapy. the use of natural adjuvants can be a promising option in reducing the toxicity of the anti-cancer agent. the aim of this study was to investigate the potential application of melatonin (mlt) as a natural adjuvant molecule along with doxorubicin (dox) to induce cytotoxicity in osteosarcoma (os) cells. methods: human os cell lines included saos-2, mg-63, and human bone marrow mesenchymal stem cells (hbm-mscs) were treated with free dox, free mlt, dox-loaded nps (dox-nps), mlt-loaded nps (mlt-nps), combination of dox and mlt (dox-mlt) and combination of dox and mlt-loaded nps (dox-mlt-nps) in separated cell culture. cell proliferation of experiments were evaluated by mtt assay after 24 h. total protein levels were determined by enzyme immunoassay elisa. results: herein, we found the combination of mlt with dox, especially formulated in nanoform, is resulted in a significant reduction in the protein levels of both x-linked inhibitor of apoptosis (xiap) and survivin (p<0.0001). indeed, there was a significant decrease in the expression of xiap and survivin when mlt is combined with dox compared to the individual treatments. conclusion: our findings indicated the synergism of the antitumor effect could be due to the down-regulation of xiap and survivin in the levels of protein.