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.