• Yin-Hwa Shih, Kuo-Chou Chiu, Tong-Hong Wang, Wan-Chen Lan, Bi-He Tsai, Li-Jia Wu, Shih-Min Hsia, and Tzong-Ming Shieh.
• Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan.
• J Formos Med Assoc. 2021 Jan 1; 120 (1 Pt 3): 668-678.

Background/PurposeArecoline, the major alkaloid of areca nut, is known to induce reactive oxygen species (ROS) and DNA damage during oral cancer progression. This study aim to evaluate whether melatonin, an antioxidant, supported or repressed the arecoline-induced carcinogenesis phenotypes in oral squamous cell carcinoma (OSCC).MethodsThe cytotoxicity of arecoline or melatonin treatment alone and their co-treatment in the OSCC cell line OEC-M1 were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle, cell death, and total ROS production were analyzed using flow cytometer. The protein expression was determined using western blot analysis. The genotoxicity and mutation rate were determined using micronucleus assay and hypoxanthine phosphoribosyl transferase (HPRT) forward mutation assay, respectively, in CHO-K1 cells. The ataxia telangiectasia mutated (ATM) promoter activity and DNA repair ability were determined through reporter assay.ResultsThe result showed that both the arecoline and melatonin induced ROS production and antioxidant enzymes expression. Melatonin treatment enhanced arecoline-induced ROS production, cytotoxicity, G2/M phase arrest, and cell apoptosis in OSCC cells. On the other hand, melatonin treatment activated DNA repair activity to reverse arecoline-induced DNA damage and mutation.ConclusionThese results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.Copyright © 2020. Published by Elsevier B.V.

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