title: Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes.
abstract: Areca (betel) was recently proved a carcinogenic substance by the International Agency for Research on Cancer. However, the signaling impact of areca in oral keratinocyte is still obscure. Mitogen-activated protein kinase superfamilies, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, together with transcription factor NF-kappaB, are important signaling elements. We examined the activation of these signaling pathways in OECM-1 and SAS oral keratinocytes, treated with ripe areca nut extract (ANE). In both cells, a rapid increase in JNK1 activity at 0.5 hr was noted following treatment of ANE. ERK was profoundly activated during 0.5-2 hr in OECM-1 cells. Contrasting p38 activity was noted in these 2 cells. In both cells, ANE also activated NF-kappaB pathway in a biphasic manner, particularly for SAS cells. NF-kappaB was activated by approximately 2- to 4-fold at 0.5-1 hr and a plateau or slight decrease of activity existed between 1 and 6 hr. Later, another higher episode of NF-kappaB activity was raised. This was accompanied with the rapid degradation in cytosolic IkappaBalpha as well as an increase of nuclear NF-kappaB in both cells. ANE treatment did not activate epidermal growth factor receptor signaling system, but blockage of NF-kappaB activation rendered the suppression of ANE-modulated COX-2 upregulation in OECM-1. This study identified that ANE affected interactive signaling systems in oral keratonocytes that could be the pathogenetic basis for areca.
authors.affiliation: Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Peitou, Taipei, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Lin
authors.forename: Suu-Yi
authors.initials: SY
authors.lastname: Lu
authors.forename: Szu-Ying
authors.initials: SY
authors.lastname: Lee
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Lin
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
mesh_terms: D001114:Areca / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000209:etiology; D018929:Cell Culture Techniques; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D006801:Humans; D015603:Keratinocytes; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009055:Mouth / Q000166:cytology; D009062:Mouth Neoplasms / Q000209:etiology; D016328:NF-kappa B / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases