| Background:
Investigationofanti-cancer agents with desirable selective toxicity is critical for cancer therapy. The use ofnatural adjuvants can be a promising option in reducing the toxicity of the anti-cancer agent. The aim ofthisstudy wasto investigatethe potential application of melatonin (MLT) as a natural adjuvantmolecule along with doxorubicin(DOX)to induce cytotoxicity in osteosarcoma (OS)cells. Methods:Human OS cell linesincluded 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 byMTT assayafter 24 h. Total protein levels weredeterminedby enzyme immunoassay ELISA .Results:Herein, we found the combination of MLT with DOX, especially formulated in nano-form, 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 findingsindicated the synergism of the antitumor effect could be due to the down-regulationofXIAPandSurvivinin the levels of protein. |