Areca nut extract upregulates vimentin by activating PI3K/AKT signaling in oral carcinoma.

Abstract

BACKGROUND:

Areca nut is a group I carcinogen. Areca nut extract (ANE) is known to activate signaling pathways in oral epithelial cells. Activation of the serine/threonine protein kinase AKT/pKB (AKT) signaling pathway is known to be important during the neoplastic process. Vimentin is a mesenchymal intermediate filament and a regulator of tumor progression. This study investigated the impact of ANE on PI3K/AKT activation during vimentin expression.

MATERIALS AND METHODS:

Oral carcinoma cells were treated with ANE to explore the signaling changes underlying vimentin expression. Oral carcinoma tissues were subjected to immunohistochemical analysis to study the implications that vimentin expression has on patient survival.

RESULTS:

After ANE treatment, the OECM-1 and Fadu cells developed a fibroblastoid morphology and there was an increase in vimentin expression. The treatment also induced the phosphorylation of AKT and glycogen synthase kinase 3β in OECM-1 cells. Blockage of phosphatidylinositol 3-kinase (PI3K)/AKT signaling attenuated vimentin expression when it was induced by ANE. However, it did not affect ANE-mediated extracellular signal-regulated kinase (ERK) activation or cyclooxygenase 2 (COX-2) upregulation. Oral carcinoma tissue samples were found to have significantly higher levels of vimentin and pAKT expression than their controls. Tumors exhibiting no vimentin expression and weak AKT phosphorylation were found to be associated with better survival than groups with high levels of expression.

CONCLUSION:

Our results imply that PI3K/AKT activation and vimentin expression are important pathogenic cascades in areca-associated oral carcinogenesis.

• Authors: Yu-Hsin Tseng, Cheng-Chieh Yang, Shu-Chun Lin, Chia-Chen Cheng, Shu-Hui Lin, Chung-Ji Liu, Kuo-Wei Chang
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 40 Issue 2 Pg. 160-6 (Feb 2011) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 21138482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Plant Extracts
• Vimentin
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Areca
• Carcinoma, Squamous Cell (metabolism, mortality)
• Cell Line, Tumor (drug effects)
• Chi-Square Distribution
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Microscopy, Confocal
• Middle Aged
• Mouth Neoplasms (metabolism, mortality)
• Nuts
• Phosphatidylinositol 3-Kinase (metabolism)
• Plant Extracts (pharmacology)
• Prognosis
• Proportional Hazards Models
• Proto-Oncogene Proteins c-akt (biosynthesis)
• Signal Transduction (drug effects)
• Up-Regulation
• Vimentin (biosynthesis)