Abstract

Melatonin, Circadian Clock and Cancer

Author(s): Rajendra Prakash Maurya

Melatonin (N-acetyl-5 methoxytryptamine) is an omnipresent naturally occurring compound widely distributed in nature, both in plants as well as animals. Dietary sources of melatonin are cereals, nuts, yeast, eggs, breast milk and fish etc. Melatonin is primarily synthesized by pineal gland and several peripheral organs such as retina, gut, skin, bone marrow and lymphocytes. The synthesis and secretion of both pineal and retinal melatonin exhibits a ‘circadian rhythm’ with higher level at night time and low levels during day hours. Circadian clocks drive such rhythms. The mammalian clocks consist of a central light-sensitive clock       (central circadian pacemaker) located in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral (cell-intrinsic) molecular clock found virtually in all nucleated cells. Molecular design of the clock is a circuit of transcription factors like CLOCK-BMAL1 which stimulates the circadian expression and PER & CRY, which suppresses CLOCK-BMAL1. The circadian clock or the circadian oscillator plays a pivotal role in regulating cellular metabolism, including mitochondrial respiration, proteostasis, autophagy, biogenesis of ribosome and DNA repair 1.Previous studies elucidated that alteration of clock components (BMAL1 & PER2) in human cancer and chronic circadian disruption through night shift/ rotating night work or trans meridian flight, may play a role in carcinogenesis, tumor growth and progression2 .Expression of clock components BMAL1 & PER2 appears to decreased in human cancer. BMAL1 could directly activate the tumor suppressor protein p53 which suppresses the tumorigenesis3.