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 Opportunities: 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 Investigator: Daniel Galera Bernabé
• Grantee: Flávia Alves Verza
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) contribute to the development of head and neck squamous cells carcinoma (HNSCC). Studies also show that NNK can induce neurotransmitter norepinephrine secretion by cells of other 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 processes are regulated by nicotinic acetylcholine receptors (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 analyzed 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.(AU)