Action of melatonin on squamous cell carcinoma and other tumors of the oral cavity (Review)

Melatonin (MLT; N-acetyl-5-metoxy-tryptamine) is a hormone that is principally synthesized in the pineal gland. MLT has been shown to exhibit a variety of functions. The hormone, which is a free radical scavenger, plays an immunomodulatory role, stimulates the proliferation and synthesis of type I collagen and promotes bone formation. Moreover, MLT exerts oncostatic activity through several biological mechanisms, including antiproliferative functions, stimulation of anticancer immunity, modulation of oncogene expression and anti-inflammatory, antioxidant and antiangiogenic effects. In addition, MLT inhibits human cancer cell growth in culture, and previous clinical studies have also confirmed its anticancer properties in vivo. With regard to the underlying mechanisms of MLT in tumor processes, including oral cavity tumors such as epidermoid carcinoma, knowledge of the role played by the MT1 and 2 membrane receptors, MT3 and the calmodulin cytosolic binding sites, as well as the nuclear receptors of the RZR/ROR family, is increasing. It has been hypothesized that exogenous restoration of MT1 (MTNR1A) expression inhibits the growth of oral squamous cell carcinoma cells lacking the expression of the receptor. The tumor suppressing functions of MLT and the presence of the MT1 receptor in various tumors indicate that the receptor may play a pivotal role in oral carcinogenesis. The current review discusses the clinical significance of MLT in oral cancer.