Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells

Tong Hong Wang, Yen Wen Shen, Hsin Ying Chen, Chih Chieh Chen, Nan Chin Lin, Yin Hwa Shih, Shih Min Hsia, Kuo Chou Chiu, Tzong Ming Shieh

Research output: Contribution to journalArticlepeer-review

Abstract

Areca nut is a major contributor to the high prevalence of oral cancer in Asia. The precise mechanisms by which areca nut stimulates mucosal cells and contributes to the progression of oral cancer urgently require clarification. The current study aimed to assess the effects of arecoline on the normal human gingival epithelium cell line S-G. Cell viability, levels of reactive oxygen species (ROS), protein expression, cellular morphology, and gene expression were evaluated using the MTT test, flow cytometry, Western blot analysis, optical or confocal microscopy, and RT-qPCR. Keratin (KRT6) analysis involved matched normal and cancer tissues from clinical head and neck specimens. The results demonstrated that 12.5 µg/mL of arecoline induced ROS production, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA expression in S-G cells. This activation of the MAPK/ERK pathway increased KRT6 expression while limiting cell migration. In head and neck cancer tissues, KRT6B gene expression exceeded that of normal tissues. This study confirms that arecoline induces ROS accumulation in normal cells, leading to the secretion of proinflammatory factors and KRT6 expression. This impedes oral mucosal healing, thereby promoting the progression of oral cancer.

Original languageEnglish
Article number412
JournalBiomedicines
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2024

Keywords

  • arecoline
  • interleukin-6
  • keratin 6
  • reactive oxygen species
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells'. Together they form a unique fingerprint.

Cite this