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Life Sci. 2018 Mar 1;196:143-155. doi: 10.1016/j.lfs.2018.01.024. Epub 2018 Jan 31.

Does the use of melatonin overcome drug resistance in cancer chemotherapy?

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Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Student Research Committee, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Mohammad@TUMS.Ac.Ir.


Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound. Reduced sensitivity and also resistance of cancer cells to antineoplastic agents are common events which might arise as a result of genomic instability of the malignant cells. Genetic mutations provide numerous mechanisms for these cells to resist cytotoxic therapies. Melatonin, due to its pleitropic effects, is able to correct these alterations in favour of sensitization to antineoplastic agents as evident by increased response to treatment via modulating the expression and phosphorylation status of drug targets, the reduced clearance of drugs by affecting their metabolism and transport within the body, decreased survival of malignant cells via altering DNA repair and telomerase activity, and enhanced responsiveness to cell death-associated mechanisms such as apoptosis and autophagy. These effects are presumably governed by melatonin's interventions in the main signal transduction pathways such as Akt and MAPK, independent of its antioxidant properties. Possessing such a signaling altering nature, melatonin can considerably affect the drug-resistance mechanisms employed by the malignant cells in breast, lung, hepatic, and colon cancers as well as different types of leukemia which are the subject of the current review.


Cancer; Chemotherapy; Drug resistance; Melatonin

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