Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma

Background/Purpose: Arecoline, 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...

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Main Authors: Yin-Hwa Shih, Kuo-Chou Chiu, Tong-Hong Wang, Wan-Chen Lan, Bi-He Tsai, Li-Jia Wu, Shih-Min Hsia, Tzong-Ming Shieh
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Journal of the Formosan Medical Association
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0929664620303491
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author Yin-Hwa Shih
Kuo-Chou Chiu
Tong-Hong Wang
Wan-Chen Lan
Bi-He Tsai
Li-Jia Wu
Shih-Min Hsia
Tzong-Ming Shieh
author_facet Yin-Hwa Shih
Kuo-Chou Chiu
Tong-Hong Wang
Wan-Chen Lan
Bi-He Tsai
Li-Jia Wu
Shih-Min Hsia
Tzong-Ming Shieh
author_sort Yin-Hwa Shih
collection DOAJ
description Background/Purpose: Arecoline, 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). Methods: The 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. Results: The 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. Conclusion: These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.
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spelling doaj.art-98035b43f33e49bda820dab26c7491d02022-12-21T19:44:26ZengElsevierJournal of the Formosan Medical Association0929-66462021-01-011201668678Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinomaYin-Hwa Shih0Kuo-Chou Chiu1Tong-Hong Wang2Wan-Chen Lan3Bi-He Tsai4Li-Jia Wu5Shih-Min Hsia6Tzong-Ming Shieh7Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; School of Dentistry, College of Dentistry, China Medical University, Taichung, TaiwanDivision of Oral Diagnosis and Family Dentistry, School of Dentistry, National Defense Medical Center, Taipei, Taiwan; School of Dentistry, College of Dentistry, China Medical University, Taichung, TaiwanTissue Bank, Chang Gung Memorial Hospital, Linko, TaiwanDepartment of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, TaiwanDepartment of Oral Hygiene, Jen-The Junior College of Medicine, Nursing and Management, Miaoli, TaiwanDepartment of Dental Hygiene, College of Health Care, China Medical University, Taichung, TaiwanSchool of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan; School of Food and Safety, Taipei Medical University, Taipei, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Corresponding author. School of Nutrition and Health Sciences, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei, 11031, Taiwan.Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan; School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan; Corresponding author. School of Dentistry, China Medical University, No. 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.Background/Purpose: Arecoline, 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). Methods: The 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. Results: The 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. Conclusion: These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.http://www.sciencedirect.com/science/article/pii/S0929664620303491ArecolineDNA repairMelatoninOral squamous cell carcinoma (OSCC)Reactive oxygen species (ROS)
spellingShingle Yin-Hwa Shih
Kuo-Chou Chiu
Tong-Hong Wang
Wan-Chen Lan
Bi-He Tsai
Li-Jia Wu
Shih-Min Hsia
Tzong-Ming Shieh
Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
Journal of the Formosan Medical Association
Arecoline
DNA repair
Melatonin
Oral squamous cell carcinoma (OSCC)
Reactive oxygen species (ROS)
title Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
title_full Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
title_fullStr Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
title_full_unstemmed Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
title_short Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma
title_sort effects of melatonin to arecoline induced reactive oxygen species production and dna damage in oral squamous cell carcinoma
topic Arecoline
DNA repair
Melatonin
Oral squamous cell carcinoma (OSCC)
Reactive oxygen species (ROS)
url http://www.sciencedirect.com/science/article/pii/S0929664620303491
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