Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Abstract

Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

<p>The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress</p>

“…11 Reportedly, the main source of melatonin is the gastrointestinal tract, with estimated production over 400 times higher than that in the pineal gland. 12 The indoleamine has great pharmacological promise as an antioxidant enzyme that can scavenge free radicals, and protect from oxidative damage. 13,14 Previous studies has shown that melatonin can inhibit the proliferation of various human cancers, including leukemia, 15,16 hepatocarcinoma, 17 breast cancer, 18 colorectal cancer, 19,20 lung cancer, 21,22 and gastric carcinoma.…”

Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction

“…Moreover, melatonin functions in the regulation of various essential events in cellular physiology, including antioxidation, anti-inflammation and immune-cell activation, and is closely related to the occurrence of multiple diseases [ 6 , 7 , 8 , 9 ], and melatonin is also produced by a few other tissues besides the pineal gland, such as the liver, skin and small intestine [ 10 , 11 ]. Melatonin regulates cell physiology through receptor-dependent and -independent mechanisms, with the regulation occurring predominantly through the receptor-dependent mechanism: By binding to the receptor MT1 (encoded by MTNR1A ) or MT2 (encoded by MTNR1B ), melatonin can activate signaling pathways in cells and regulate physiological processes such as inflammation and the immune response [ 12 , 13 , 14 ]. Furthermore, melatonin and its metabolites are potent antioxidants that can bind directly to and neutralize peroxides produced in metabolism and thereby reduce cellular damage and act as powerful free-radical scavengers [ 15 , 16 , 17 ].…”

Effects of Melatonin on Chronic Pancreatitis and Atherosclerosis

“…-мелатонін пригнічує утворення ендотеліальних молекул адгезії, -зменшує жирову інфільтрацію ендотелію, -нейтралізує вільні радикали, -зменшує перекисне окиснення ліпідів, -модулює кліренс холестерину, -запобігає витоку електронів з дихального ланцюга мітохондрій [6,7].…”