Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Life Sci. 2021 Feb 15;267:118934. doi: 10.1016/j.lfs.2020.118934. Epub 2020 Dec 29.
The biological functions of melatonin range beyond the regulation of the circadian rhythm. With regard to cancer, melatonin's potential to suppress cancer initiation, progression, angiogenesis and metastasis as well as sensitizing malignant cells to conventional chemo- and radiotherapy are among its most interesting effects. The targets at which melatonin initiates its anti-cancer effects are in common with those of a majority of existing anti-cancer agents, giving rise to the notion that this molecule is a pleiotropic agent sharing many features with other antineoplastic drugs in terms of their mechanisms of action. Among these common mechanisms of action are the regulation of several major intracellular pathways including mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and protein kinase B (AKT/PKB) signaling. The important mediators affected by melatonin include cyclins, nuclear factor-κB (NF-κB), heat shock proteins (HSPs) and c-Myc, all of which can serve as potential targets for cancer drugs. Melatonin also exerts some of its anti-cancer effects via inducing epigenetic modifications, DNA damage and mitochondrial disruption in malignant cells. The regulation of these mediators by melatonin mitigates tumor growth and invasiveness via modulating their downstream responsive genes, housekeeping enzymes, telomerase reverse transcriptase, apoptotic gene expression, angiogenic factors and structural proteins involved in metastasis. Increasing our knowledge on how melatonin affects its target sites will help find ways of exploiting the beneficial effects of this ubiquitously-acting molecule in cancer therapy. Acknowledging this, here we reviewed the most studied target pathways attributed to the anti-cancer effects of melatonin, highlighting their therapeutic potential.
褪黑素的生物学功能不仅限于调节昼夜节律。就癌症而言，褪黑素具有抑制癌症发生、进展、血管生成和转移的潜力，以及使恶性细胞对常规化疗和放疗敏感的潜力，这些都是其最有趣的作用之一。褪黑素引发其抗癌作用的靶点与大多数现有抗癌药物的靶点相同，这使得人们认为这种分子是一种多效剂，在作用机制方面与其他抗肿瘤药物有许多共同特征。这些共同的作用机制包括调节几种主要的细胞内途径，包括有丝分裂原激活的蛋白激酶（MAPK）、细胞外信号调节激酶（ERK）和蛋白激酶 B（AKT/PKB）信号通路。受褪黑素影响的重要介质包括细胞周期蛋白、核因子-κB（NF-κB）、热休克蛋白（HSPs）和 c-Myc，它们都可以作为潜在的癌症药物靶点。褪黑素还通过诱导恶性细胞中的表观遗传修饰、DNA 损伤和线粒体破坏来发挥其部分抗癌作用。褪黑素对这些介质的调节通过调节其下游反应基因、管家酶、端粒酶逆转录酶、凋亡基因表达、血管生成因子和参与转移的结构蛋白来减轻肿瘤生长和侵袭性。增加我们对褪黑素如何影响其靶位点的了解将有助于找到利用这种广泛作用的分子在癌症治疗中的有益作用的方法。鉴于此，我们在这里回顾了与褪黑素抗癌作用相关的研究最多的靶途径，强调了它们的治疗潜力。
