Areca nut extract treatment elicits the fibroblastoid morphological changes, actin re-organization and signaling activation in oral keratinocytes.
BACKGROUND
Areca (named as betel) is an important etiological factor linked with the high prevalence of oral squamous cell carcinoma (OSCC) in South-Asian countries. This in vitro study investigated the cellular changes and signaling activation in oral keratinocytes in response to areca nut extract (ANE) treatment.


METHODS
Normal human oral keratinocyte (NHOK) and oral epidermoid carcinoma cell, Meng-1 (OECM-1) OSCC cell line were treated with variable dosages of ripen ANE. The morphological and cytoskeletal changes, as well as the activation of GTPase proteins and signaling kinases, were analyzed.


RESULTS
Most NHOK cells in culture were polygonal, with only <5% cells exhibiting fibroblastoid morphology. However, 10 microg/ml ANE elicited fibroblastoid morphological change, genesis of lamellipodia, loss of subcortical actin, and stress-fiber formation in approximately 25% cultivated NHOK cells. Similar morphological changes were observed in nearly all OECM-1 cells following the ANE treatment. The activation of Rac and Rho GTPase, together with the prominent phosphorylation of a stress-activated kinases, particularly JNK1, was identified in treated OECM-1 cells.


CONCLUSIONS
The novel evidences from the study that ANE impairs the actin organization and activates the signals in oral keratinocytes might bestow further insight into the impacts of ANE in oral pathogenesis.
Yang
Shun-Chun
SC
Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Taiwan.
Lin
Shu-Chun
SC
Chiang
Wei-Fan
WF
Yen
Ching-Yu
CY
Lin
Chi-Hung
CH
Liu
Shyun-Yeu
SY
D000199:Actins / Q000032:analysis / Q000187:drug effects*; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D020549:GTP Phosphohydrolase Activators / Q000032:analysis; D020690:GTPase-Activating Proteins / Q000032:analysis / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000187:drug effects*; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis / Q000187:drug effects; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000473:pathology; D009754:Nuts; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000032:analysis / Q000187:drug effects
D000199:Actins; D020549:GTP Phosphohydrolase Activators; D020690:GTPase-Activating Proteins; D010936:Plant Extracts; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins