Melatonin and Cancer: A Polyhedral Network Where the Source Matters

Abstract

Melatonin is one of the most phylogenetically conserved signals in biology. Although its original function was probably related to its antioxidant capacity, this indoleamine has been “adopted” by multicellular organisms as the “darkness signal” when secreted in a circadian manner and is acutely suppressed by light at night by the pineal gland. However, melatonin is also produced by other tissues, which constitute its extrapineal sources. Apart from its undisputed chronobiotic function, melatonin exerts antioxidant, immunomodulatory, pro-apoptotic, antiproliferative, and anti-angiogenic effects, with all these properties making it a powerful antitumor agent. Indeed, this activity has been demonstrated to be mediated by interfering with various cancer hallmarks, and different epidemiological studies have also linked light at night (melatonin suppression) with a higher incidence of different types of cancer. In 2007, the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption, where melatonin plays a central role. Our aim is to review, from a global perspective, the role of melatonin both from pineal and extrapineal origin, as well as their possible interplay, as an intrinsic factor in the incidence, development, and progression of cancer. Particular emphasis will be placed not only on those mechanisms related to melatonin’s antioxidant nature but also on the recently described novel roles of melatonin in microbiota and epigenetic regulation.

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…Circadian rhythm clock genes play a critical role during neurodegenerative disorders and dementia [8,31,72-78] (Table 1). In addition, circadian clock genes affect metabolic disease and cell injury [8, [78][79][80][81][82][83][84][85][86][87], cell cycle regulation [88][89][90][91], cancer [82,83,[92][93][94], energy metabolism and aging [72,76,79,86,95], mitochondrial energy maintenance [78,83,96,97], renal disease [80,92], and viral diseases [74,[98][99][100][101][102][103][104][105][106]. The mammalian circadian clock, located in the suprachiasmatic nucleus (SCN) located above the optic chiasm, receives light input from photosensitive ganglion cells in the retina [8,86,103].…”

“…The mammalian circadian clock, located in the suprachiasmatic nucleus (SCN) located above the optic chiasm, receives light input from photosensitive ganglion cells in the retina [8,86,103]. The SCN controls melatonin and cortisol release, the temperature of the body, and can respond to oxidative stress [94,107,108]. The basic helix-loop-helix -PAS (Period-Arnt-Single-minded) transcription factor family oversee Cryptochrome (Cry1 and Cry2) and Period (Per1, Per2, and Per3) genes [8, 80,86,92,[109][110][111].…”

“…Processes that are involved with aging and cognitive loss are dependent upon melatonin, a pineal hormone that controls circadian rhythm [83,94,100], and mTOR in conjunction with autophagy induction [95,175]. Melatonin and the control of the circadian cycle can during aging can be affected infection such as with COVID-19 [99], cellular metabolism [95,108], mitochondrial dysfunction [83], oxidative stress [176,177], and inflammatory mediators [175,178].…”

Ritmo circadiano y cáncer, o cómo la evolución nos adaptó a nuestro entorno

“…Figura: Esquema de la organización del sistema circadiano (Modificado de Bonmati-Carrión y Tomás-Loba, 2021) 8…”

Correlated color temperature and light intensity: Complementary features in non-visual light field

“…Interestingly, although all M1 ipRGCs are morphologically and electrophysiologically similar, these two molecularly different subpopulations coexist and innervate different brain regions: M1 Brn3b-for SCN and M1 Brn3b+ for OPN [17]. Among all output pathways, pineal melatonin secretion is the best characterized rhythm, with a peak during the night and lower levels during the day [18][19][20][21]. This hormone exerts a prominent chronobiotic function and, in humans, also plays an important role in sleep promotion [22].…”