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Elevated snail expression mediates tumor progression in areca quid chewing-associated oral squamous cell carcinoma

Shiuan-Shinn Lee1, Chung-Hung Tsai, Cheng-Chia Yu

  • 1School of Public Health, Chung Shan Medical University, Taichung, Taiwan.

Plos One
|July 23, 2013
PubMed
Abstract

Insights

Areca nut alkaloid arecoline induces Snail expression, a key factor in oral cancer progression, through reactive oxygen species (ROS). Antioxidants like curcumin can inhibit this process, offering potential therapeutic insights for oral squamous cell carcinoma (OSCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Carcinogenesis

Background:

  • Snail is a transcription factor involved in tumor progression, inducible by reactive oxygen species (ROS).
  • Areca quid chewing is a significant risk factor for oral squamous cell carcinoma (OSCC).

Purpose of the Study:

  • To investigate if arecoline, the main alkaloid in areca nuts, induces Snail expression via ROS.
  • To explore the role of arecoline-induced Snail in the pathogenesis of OSCC associated with areca quid chewing.

Main Methods:

  • Immunohistochemistry was used to analyze Snail expression in OSCC and normal oral tissues.
  • In vitro studies examined the effects of arecoline on human oral keratinocytes (HOKs) and OECM-1 cells, assessing ROS generation and Snail expression.
  • Antioxidants (NAC, curcumin, EGCG) were used to investigate regulatory mechanisms.

Main Results:

  • Snail expression was significantly higher in OSCC tissues and associated with lymph node metastasis and poor differentiation.
  • Arecoline increased intracellular ROS and induced Snail expression in a dose- and time-dependent manner.
  • Antioxidants NAC, curcumin, and EGCG inhibited arecoline-induced Snail expression.

Conclusions:

  • Snail overexpression in areca quid-associated OSCC correlates with tumor differentiation and metastasis.
  • Arecoline-induced Snail upregulation is likely mediated by ROS generation.
  • Antioxidants effectively downregulate arecoline-induced Snail expression, suggesting a potential therapeutic strategy.

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