Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma.
Arecoline
DNA repair
Melatonin
Oral squamous cell carcinoma (OSCC)
Reactive oxygen species (ROS)
Journal
Journal of the Formosan Medical Association = Taiwan yi zhi
ISSN: 0929-6646
Titre abrégé: J Formos Med Assoc
Pays: Singapore
ID NLM: 9214933
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
20
06
2020
revised:
21
07
2020
accepted:
28
07
2020
pubmed:
18
8
2020
medline:
26
2
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
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). 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. 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. These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.
Sections du résumé
BACKGROUND/PURPOSE
OBJECTIVE
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
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
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
CONCLUSIONS
These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.
Identifiants
pubmed: 32800657
pii: S0929-6646(20)30349-1
doi: 10.1016/j.jfma.2020.07.037
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Arecoline
4ALN5933BH
Melatonin
JL5DK93RCL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
668-678Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no conflicts of interest to declare.