Arecoline-mediated inhibition of AMP-activated protein kinase through reactive oxygen species is required for apoptosis induction

Ching Yu Yen, Mei Huei Lin, Shyun Yeu Liu, Wei Fan Chiang, Wan Fang Hsieh, Yon Chi Cheng, Kai Cheng Hsu, Young Chau Liu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Arecoline is the major alkaloid of areca nut (AN) and known to induce reactive oxygen species (ROS) production and apoptosis. The metabolic sensor AMP-activated protein kinase (AMPK), activated by ROS, also regulates apoptosis. This study used several types of cells as the experimental model to analyze the roles of ROS and AMPK in arecoline-induced apoptosis. We found that arecoline dose-dependently increased intracellular ROS level, and two antioxidants, N-acetyl-l-cysteine (NAC) and glutathione, attenuated arecoline-induced apoptotic cell death. Interestingly, arecoline dose- and time-dependently inhibited rather than stimulated AMPK-Thr172 phosphorylation, and both NAC and glutathione relieved this inhibition. The AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), also restored the phosphorylation level of AMPK-Thr172 and attenuated apoptotic cell death under arecoline insult. In contrast, the AMPK inhibitor, compound C, and RNA interference of AMPK expression increased the cytotoxicity of arecoline. Collectively, these results suggest that arecoline may inhibit AMPK through intracellular ROS, responsible for the execution of apoptosis.

Original languageEnglish
Pages (from-to)345-351
Number of pages7
JournalOral Oncology
Volume47
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • AMPK
  • Apoptosis
  • Areca nut
  • Arecoline
  • ROS

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

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