Hsi-Feng Tu1,2, Michael Yuanchien Chen3,4, Joseph Chieh-Yui Lai5, Yi-Ling Chen5, Yih-Wen Wong4, Cheng-Chieh Yang1,6, Hsin-Yuan Chen7, Shih-Min Hsia7,8,9,10, Yin-Hwa Shih11, Tzong-Ming Shieh5. 1. Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan. 2. Department of Dentistry, National Yang-Ming University Hospital, Yilan, Taiwan. 3. Department of Oral & Maxillofacial Surgery, China Medical University Hospital, Taichung, Taiwan. 4. School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan. 5. Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan. 6. Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan. 7. School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan. 8. Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan. 9. School of Food and Safety, Taipei Medical University, Taipei, Taiwan. 10. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan. 11. Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Abstract
BACKGROUND: Ataxia telangiectasia mutated (ATM) regulates DNA repair and cell cycle. The present study analyzed arecoline-induced ATM expression during oral cancer progression. METHODS: In vitro studies were performed using oral squamous cell carcinoma (OSCC) cell lines treated with arecoline to analyze cell response and ATM regulation. in vivo studies were performed using immunohistochemistry to detect ATM expression in normal, oral potentially malignant disorder (OPMD), and OSCC tissues. RESULTS: Low-dose arecoline induced cell proliferation, ATM promoter activity, and DNA repair. High-dose arecoline induced cell cycle arrest, apoptosis, and DNA damage. ATM was overexpressed in OPMD tissues but was downregulated in OSCC tissues. ATM expression level was associated with the risk of developing dysplasia, buccal-OSCC, and with OSCC survival rate. CONCLUSION: High ATM expression helps DNA repair mechanisms to maintain the cells in the OPMD stage, but low ATM expression causes DNA damage accumulation to increase cell malignancy.
BACKGROUND:Ataxia telangiectasia mutated (ATM) regulates DNA repair and cell cycle. The present study analyzed arecoline-induced ATM expression during oral cancer progression. METHODS: In vitro studies were performed using oral squamous cell carcinoma (OSCC) cell lines treated with arecoline to analyze cell response and ATM regulation. in vivo studies were performed using immunohistochemistry to detect ATM expression in normal, oral potentially malignant disorder (OPMD), and OSCC tissues. RESULTS: Low-dose arecoline induced cell proliferation, ATM promoter activity, and DNA repair. High-dose arecoline induced cell cycle arrest, apoptosis, and DNA damage. ATM was overexpressed in OPMD tissues but was downregulated in OSCC tissues. ATM expression level was associated with the risk of developing dysplasia, buccal-OSCC, and with OSCC survival rate. CONCLUSION: High ATM expression helps DNA repair mechanisms to maintain the cells in the OPMD stage, but low ATM expression causes DNA damage accumulation to increase cell malignancy.