Melatonin as an oncostatic agent: Review of the modulation of tumor microenvironment and overcoming multidrug resistance.

Multi drug resistance (MDR) generally limits the efficacy of chemotherapy in cancer patients and can be categorized into primary or acquired resistance. Melatonin (MLT), a lipophilic hormone released from pineal gland, is a molecule with oncostatic effects. Here, we will briefly review the contribution of different microenvironmental components including fibroblasts, immune and inflammatory cells, stem cells and vascular endothelial cells in tumor initiation, progression and development. Then, the mechanisms by which MLT can potentially affect these elements and regulate drug resistance will be presented. Finally, we will explain how different studies have used novel strategies incorporating MLT to suppress cancer resistance against therapeutics.