Epidemiology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131 Napoli, Italy.
Experimental Pharmacology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131 Napoli, Italy.
Molecules. 2018 May 29;23(6):1308. doi: 10.3390/molecules23061308.
In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock's genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types.
在哺乳动物中,主钟位于下丘脑的视交叉上核(SCN)内,该区域接收来自视网膜的输入,这些输入通过视网膜下丘脑束进行传输。SCN 控制松果腺在夜间合成褪黑素,褪黑素可以影响时钟基因的活性,并参与抑制癌症的发展。另一方面,在文献中,一些论文强调夜间人工光照(LAN)引起的昼夜节律紊乱会促进癌症的发生。在本综述中,我们总结了 LAN 引发的褪黑素合成夜间增加中断的潜在机制,这些机制抵消了其对人类癌症发展和进展的预防作用。具体而言,我们讨论了:(i)与肿瘤代谢改变相关的沃伯格效应;(ii)与 L1 活性相关的基因组不稳定性;以及(iii)免疫调节,包括调节性 T 细胞(Treg)调节和活性。对这些过程的更好理解可能会极大地促进针对激素相关癌症类型的新的治疗和预防策略。