Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics

Abstract

The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.

FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis

“…Importantly, MT has shown to be an endogenously generated agent helpful in cancer prevention and treatment due to its low toxicity [ 15 , 16 ]. A good example is that MT can be used as a potential adjuvant treatment in oral cancer therapy [ 11 ]. Although most experts advise to avoid extremely high dosages of MT, there is no consensus about its effective dose in cancer management [ 23 , 24 ].…”

“…Melatonin (MT) is a methoxyindole synthesized and released by the pineal gland and other extrapineal sources, including the oral cavity and the salivary glands [9][10][11]. There is highly credible evidence outlining the relevance of MT to human physiology and pathology.…”

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

“…Mainly, among the most significant actions of supplemented melatonin described to date, we must highlight its antioxidant, free-radical scavenging, immunomodulatory, and anti-inflammatory activity, which makes melatonin a powerful tool in the treatment of any disease that involves one or more of these components. There is an increasing interest in melatonin against cancer; recent studies report a very promising oncostatic profile of melatonin in several types of cancer and associated effects that seem to enhance chemotherapy [72][73][74][75][76].…”

Exosomes and Melatonin: Where Their Destinies Intersect

“…The oral squamous cell carcinoma (OSCC) and epidermoid oral carcinoma are the most frequent malignant cancers, representing 90-95% of cases. The challenging paradigm is due to the worse prognosis and high mortality rate, combined with the lack of better perspectives (65). Differential microRNA (miRNA) expression profile in OSCCrelated EVs have been documented both in vitro and in clinical experiments (66,67).…”