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Analysis of the effect of tobacco derived carcinogen NNK on norepinephrine production and oral cancer cells proliferation: role of the beta-adrenergic and nicotinic acetylcholine receptors

Grant number: 13/24661-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2014
Effective date (End): November 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Daniel Galera Bernabé
Grantee:Flávia Alves Verza
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


The nicotine derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) contributes to development of head and neck squamous cells carcinoma (HNSCC). Studies also show that NNK can induce neurotransmitter norepinephrine secretion by cells of others cancer, but this mechanism has not been investigated in oral SCC cells. Recently, we showed that norepinephrine induces cell proliferation of OSCC cells. Here, we will investigate the effects of NNK on the norepinephrine secretion by OSCC and proliferation as also these process are regulated by nicotinic acetylcholine receptor (nAChRs) and beta-adrenergic receptors. The OSCC cell lines SCC9 and SCC25 and normal oral mucosal keratinocytes (HaCaT) will be stimulated with NNK at different concentrations. The effects of NNK on the beta-adrenergic receptor type 1 and 2 and nAChRs type ±4 and ±7 expression in SCC9, SCC25 and HaCaT cells will be analysed by PCR real time. The effects of NNK on SCC9 and SCC25 cell proliferation will be evaluated by BrdU incorporation assay. Tests with specific antagonists (± - bungarotoxin for nAChRs receptors and propranolol for beta-adrenergic receptors) will be carried out to investigate the role of these receptors on the NNK-induced effects, if it occurs.