Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma
Department of Orthopedics, Chung Shan Medical University Hospital, Taichung 402, Taiwan
School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Division of Hyperbaric Oxygen Therapy and Wound Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Department of Cell Systems and Anatomy, UT Health, San Antonio, TX 78229, USA
Authors to whom correspondence should be addressed.
Cells 2019, 8(12), 1618; https://doi.org/10.3390/cells8121618
Received: 26 November 2019 / Revised: 6 December 2019 / Accepted: 9 December 2019 / Published: 12 December 2019
(This article belongs to the Special Issue Melatonin in Human Health and Diseases)
Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11–15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes. While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma. Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines. We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis. Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma. As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.