Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

Abstract

For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.

Is an Entropy-Based Approach Suitable for an Understanding of the Metabolic Pathways of Fermentation and Respiration?

“…In addition, for the same tissue we have taken an average size of the intercellular space about 0.2-0.3 µm between two adjacent normal cells and about 1.5 µm between two cancer cells [40]. cells, the glucose catabolism is 80% through OXPHOs and 20% through lactic acid fermentation, while in cancer cells 90% occurs through lactic acid fermentation and 10% through OXPHOs [32]. Both respiration and lactic acid fermentation are first-order processes.…”

“…ri D was calculated according to Equation (3), while ri r was calculated according to Equation (4). We have taken Nresp = 4 (Nferm = 3), the number of chemical species involved in the respiration (fermentation) process, wresp = 0.8 (wferm = 0.2) for a normal cell and wresp = 0.1 (wferm = 0.9) for a cancer cell [32,33]. In addition, the partial molar energies or chemical potentials at t = 0 and x = L/2, at standard conditions, used in the numerical calculations were: μC6H12O6 = −917.…”

“…Nevertheless, even though the study of the metabolic network and of the dynamical aspects of the mitochondria network has received a great attention, there are only few thermodynamic descriptions of metabolism [25][26][27][28][29][30][31][32][33]. For this reason, in [34] we have developed a thermodynamic model to calculate the rate of entropy density production for irreversible reactions in living systems.…”

Design and validation of the first cell‐impermeant melatonin receptor agonist

“…Melatonin receptors and its cell‐penetrating ligand (melatonin) are excellent candidates for such a scenario. Indeed, melatonin has well‐established protective effects on mitochondrial energy metabolism and on limiting oxidative stress (Pacini and Borziani, ), but the underlying molecular mechanisms are unknown. A recent study suggests that the MT 1 receptor is located in brain mitochondria (Wang et al , ).…”

Beneficial role of melatonin in protecting mammalian gametes and embryos from oxidative damage

“…Melatonin (N-acetyl-5-methoxytryptamine) was discovered as a secretory product of the pineal gland and is now known to be generated in many, perhaps all, organs in the body (Reiter et al 2013(Reiter et al , 2014. Melatonin has been found to have multiple physiological functions; it exhibits a synchronous circadian rhythm and is involved in sleep modulation (Arendt 2000;Fisher et al 2008), seasonal reproductive regulation (Reiter et al 2009b), blood pressure reduction (Reiter et al 2009a), immune stimulation (Carrillo-Vico et al 2006), inflammatory inhibition (Manka and Majewska 2016), and oncostatic/cytoprotective actions (Pacini and Borziani 2016). The lipophilic and hydrophilic properties of melatonin permit it to rapidly pass through all morphophysiological barriers with ease and distribute in other organs and fluids (Tamura et al 2012;Cruz et al 2014a).…”