دانلود رایگان مقاله انگلیسی غلبه استفاده از ملاتونین بر مقاومت دارو در شیمی درمانی سرطان - الزویر 2018

ABSTRACT

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.

10. Concluding remarks

Reports from the studies so far demonstrate that melatonin possesses the capability to sensitize various cancers, such as breast, lung, colon, hepatic, and hematologic cancers to the effects of antineoplastic agents like anthracyclines, alkylating agents, tyrosine kinase inhibitors, endogenous factors such as TNF-α, TRAIL, and FAS, as well as ionizing radiation. Melatonin involves a collection of mechanisms in overcoming resistance and sensitization of cancer cells; (a) modulation of target receptors of drugs, (b) reduction of cellular clearance of medications by downregulation of transport mechanisms and metabolizing enzymes (c) impairment of DNA repair (d) enhancement of programmed cell death via apoptosis and autophagy (e) modulation of signal transduction pathways involved in promotion of survival. The pleiotropic actions of melatonin are particularly valuable since cancer cells commonly employ multiple mechanisms for their survival and resistance to therapy. The ability of melatonin to selectively sensitize cancer cells to cytotoxic therapies while protecting normal cells from toxicities of such agents, warrant its consideration as a potential adjuvant to cancer treatment and further research in this field is encouraged.