Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment

Abstract

Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro-oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology. K E Y W O R D S apoptosis, chemotherapy, DNA damage, melatonin, oncology, mitochondria, genomic instability, radiotherapy

Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

“…Melatonin (N-acetyl-5-methoxytryptamine), which is synthesized by the pineal gland and many other organs, is a neuroendocrine hormone 28,29 that is involved in a wide range of physiological functions, including anti-inflammatory, 30,31 antidegenerative, 32,33 antioxidant, 34,35 immunomodulatory, 36,37 circadian rhythm regulation, 38 and cancer prevention activities. [39][40][41][42] Notably, recent studies have demonstrated that melatonin attenuates the inflammatory response by inhibiting NLRP3 inflammasome activation during the progression of atherosclerosis 43 and brain, 44 liver 45 and lung diseases. 46 Moreover, melatonin plays crucial roles in the IVDD process, including regulating NP cell proliferation, remodeling the ECM, 47 protecting vertebral endplate chondrocytes against apoptosis and calcification, 48 and preventing oxidative stress-induced NP cell apoptosis, 49 indicating a strong correlation between melatonin and IVDD.…”

Resveratrol targeting the Wnt signaling pathway: A focus on therapeutic activities

“…In spite of much progress in cancer treatment and prevention, it is still one of the leading causes of death around the world and is considered as the second cause of death in the US. Furthermore, there is a lack of precise approaches to detect cancer in early stages, resulting in difficulties in treatment of cancer due to resistance of cancer cells to chemotherapy and antitumor drugs in advanced stages (Ashrafizadeh, Mohammadinejad et al, ; Farhood et al, ; Mohammadinejad, Dadashzadeh et al, ; Salmaninejad et al, ). A major problem of uterine sarcoma is its poor prognosis.…”

Melatonin: A promising agent targeting leukemia

“…In this regard, NO can induce the accumulation of DNA damage and the promotion of genomic instability . It has been shown that melatonin accelerates the kinetics of DNA repair following exposure of DNA to ROS . Hence, it seems that melatonin could be used as an anticancer agent in the treatment of various cancers, such as leukemia.…”

“…70,[79][80][81][82] Besides the direct action of melatonin, this agent enables neutralizing free radicals through induction of suppression of redox enzyme activity (DUOX1&2, NOX2&4, iNOS, and mitochondria derived ROS) or antioxidant enzymes. 76 Therefore, these features make melatonin a potential therapeutic agent for radioprotection during radiotherapy or exposure to nuclear or radiological pollutants or warfare. 75,76 One of the main physiological and antitumor functions of melatonin is the modulation of linoleic acid uptake and metabolism in tumor cells.…”

“…76 Therefore, these features make melatonin a potential therapeutic agent for radioprotection during radiotherapy or exposure to nuclear or radiological pollutants or warfare. 75,76 One of the main physiological and antitumor functions of melatonin is the modulation of linoleic acid uptake and metabolism in tumor cells. 83…”