Areca (betel) nut extract activates mitogen-activated protein kinases and NF-κB in oral keratinocytes

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-...

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Bibliographic Details
Published in:International journal of cancer 2005-09, Vol.116 (4), p.526-535
Main Authors: LIN, Shu-Chun, LU, Suu-Yi, LEE, Szu-Ying, LIN, Chi-Yen, CHEN, Chun-Hsien, CHANG, Kuo-Wei
Format: Article
Language:English
Subjects:
Areca catechu
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Foods and miscellaneous
Medical sciences
Tumors
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Summary: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- Kappa B, 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- Kappa B pathway in a biphasic manner, particularly for SAS cells. NF- Kappa B was activated by ~ 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- Kappa B activity was raised. This was accompanied with the rapid degradation in cytosolic I Kappa B alpha as well as an increase of nuclear NF- Kappa B in both cells. ANE treatment did not activate epidermal growth factor receptor signaling system, but blockage of NF- Kappa B 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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.21104