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

Yin Hwa Shih, Kuo Chou Chiu, Tong Hong Wang, Wan Chen Lan, Bi He Tsai, Li Jia Wu, Shih Min Hsia, Tzong Ming Shieh

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)668-678
Number of pages11
JournalJournal of the Formosan Medical Association
Issue number1
Publication statusPublished - Jan 2021


  • Arecoline
  • DNA repair
  • Melatonin
  • Oral squamous cell carcinoma (OSCC)
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Medicine(all)


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