Pharmaceutical Sciences (Jun 2020)

The Sensitization of Melatonin in Osteosarcoma Cells by Suppression of Anti-Apoptotic Proteins

  • Seyed Mostafa Mir,
  • Bahman Yousefi,
  • Abdoljalal Marjani,
  • Mahdi Rahimi,
  • Durdi Qujeq

DOI
https://doi.org/10.34172/PS.2020.3
Journal volume & issue
Vol. 26, no. 2
pp. 159 – 164

Abstract

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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 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 findings indicated the synergism of the antitumor effect could be due to the down-regulation of XIAP and Survivin in the levels of protein.

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