Asghari Mohammad Hossein, Ghobadi Emad, Moloudizargari Milad, Fallah Marjan, Abdollahi Mohammad
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.
Life Sci. 2018 Mar 1;196:143-155. doi: 10.1016/j.lfs.2018.01.024. Epub 2018 Jan 31.
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.
我们对于褪黑素在包括癌症在内的众多医学病症治疗中的作用的认识正在不断扩展。褪黑素可通过针对任何肿瘤病症的几个关键方面，包括致癌作用的起始以及肿瘤的生长、分化和扩散，以多种方式影响癌症病理。许多研究已在各种癌症背景下考察了褪黑素的作用，报告了其与化疗/放疗联合使用时疗效增强。癌细胞对抗肿瘤药物的敏感性降低以及产生耐药性是常见现象，这可能是由于恶性细胞的基因组不稳定所致。基因突变提供了这些细胞抵抗细胞毒性疗法的多种机制。褪黑素由于其多效性作用，能够纠正这些改变，有利于对抗肿瘤药物产生敏感性，这表现为通过调节药物靶点的表达和磷酸化状态提高对治疗的反应、通过影响药物在体内的代谢和转运减少药物清除、通过改变DNA修复和端粒酶活性降低恶性细胞的存活率以及增强对细胞死亡相关机制（如凋亡和自噬）的反应性。这些作用大概是由褪黑素对诸如Akt和MAPK等主要信号转导途径的干预所介导的，与其抗氧化特性无关。由于具有这种信号改变性质，褪黑素可显著影响乳腺癌、肺癌、肝癌和结肠癌以及不同类型白血病中恶性细胞所采用的耐药机制，这些是本综述的主题。
