Role and Therapeutic Potential of Melatonin in Various Type of Cancers

Sangiliyandi Gurunathan,¹ Muhammad Qasim,² Min-Hee Kang,¹ Jin-Hoi Kim<sup>1

1</sup>Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea; ²Center of Bioengineering and Nanomedicine, Department of Food Science, University of Otago, Dunedin, 9054, New Zealand

Correspondence: Jin-Hoi Kim
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea
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Abstract: Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors. In this manuscript, we will comprehensively review some of the cellular, animal, and human studies from the literature that provide evidence that melatonin has oncostatic and anticancer properties. Further, this comprehensive review compiles the available experimental and clinical data analyzing the history, epidemiology, risk factors, therapeutic effect, clinical significance, of melatonin alone or in combination with chemotherapeutic agents or radiotherapy, as well as the underlying molecular mechanisms of its anticancer effect against lung, breast, prostate, colorectal, skin, liver, cervical, and ovarian cancers. Nonetheless, in the interest of readership clarity and ease of reading, we have discussed the overall mechanism of the anticancer activity of melatonin against different types of cancer. We have ended this report with general conclusions and future perspectives.

Keywords: melatonin receptors, antioxidant, antiangiogenic, anticancer, apoptosis, angiogenesis, metastasis, chemotherapy, combination therapy, molecular mechanisms