Samanta Saptadip
Department of Physiology, Midnapore College, Midnapore, Paschim Medinipur 721101, West Bengal, India.
Crit Rev Oncog. 2021;26(3):53-67. doi: 10.1615/CritRevOncog.2021041260.
Melatonin is an endogenous indolamine, synthesized and secreted from the pineal gland. The environmental light-dark cycle is the primary regulator of melatonin synthesis. Darkness during the subjective night induces noradrenaline secretion, which stimulates pinealocytes for melatonin production. Melatonin exhibits anticancer effects and different physiological functions through the membrane-bound G-protein-coupled MT1 and MT2 receptors. Impaired circadian activity, indoor or outdoor light pollution, shift work, night work, and jet lag suppress normal melatonin synthesis. Decreased melatonin concentration causes impaired anticancer effects that adversely affect the progression of different cancers, including prostate. Melatonin differentially regulates the cell cycle, cell survival, and metabolism in malignant cells in contrast to normal prostate epithelial cells. Melatonin promotes the nuclear exclusion of androgen receptors without suppressing the expression of this receptor. This indirect effect blocks the androgenic response in prostate cancer cells. It acts as a cytostatic and cytotoxic agent, prevents cell proliferation, and activates an apoptotic response. Melatonin also inhibits HIF-1α activity and the expression of vascular endothelial growth factors to suppress angiogenesis. This indolamine restricts alteration of metabolic activity, invasion, and metastasis. Melatonin has therapeutic importance. It decreases the side effects of anticancer treatment and mitigates adverse effects after prostatectomy and radiotherapy. Melatonin blocks the recurrence of prostate cancer as well as hormone-refractory effects during androgen deprivation therapy. The present review discusses the multifaceted effects of melatonin against prostate cancer.
褪黑素是一种内源性吲哚胺，由松果体合成和分泌。环境光暗周期是褪黑素合成的主要调节因子。主观夜间的黑暗会诱导去甲肾上腺素分泌，刺激松果体细胞产生褪黑素。褪黑素通过膜结合的G蛋白偶联的MT1和MT2受体发挥抗癌作用和不同的生理功能。昼夜节律活动受损、室内或室外光污染、轮班工作、夜间工作和时差反应会抑制正常的褪黑素合成。褪黑素浓度降低会导致抗癌作用受损，对包括前列腺癌在内的不同癌症的进展产生不利影响。与正常前列腺上皮细胞相比，褪黑素对恶性细胞的细胞周期、细胞存活和代谢有不同的调节作用。褪黑素促进雄激素受体核排除而不抑制该受体的表达。这种间接作用阻断了前列腺癌细胞中的雄激素反应。它作为一种细胞生长抑制剂和细胞毒性剂，阻止细胞增殖，并激活凋亡反应。褪黑素还抑制HIF-1α活性和血管内皮生长因子的表达以抑制血管生成。这种吲哚胺限制代谢活性、侵袭和转移的改变。褪黑素具有治疗意义。它可降低抗癌治疗的副作用，并减轻前列腺切除术后和放疗后的不良反应。褪黑素可阻断前列腺癌的复发以及雄激素剥夺治疗期间的激素抵抗效应。本综述讨论了褪黑素对前列腺癌的多方面作用。
