NUMERO: #20240982

Título: TOBACCO CARCINOGEN NNK INDUCE ORAL CANCER CELLS PROLIFERATION THROUGH A ADRENERGIC-RELATED PATHWAY

Nome do Apresentador: Ana Lívia SANTOS-SOUSA

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Oncologia

Resumo: Purpose: Although a growing number of studies demonstrate the impact of stress-related catecholamines on oral cancer progression, no studies have investigated whether tobacco-related nitrosamines can modulate catecholamine production and cell proliferation in oral squamous cell carcinoma (OSCC). Methods: In this study we investigated the effects of the tobacco carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the norepinephrine (NE) secretion and proliferation of keratinocytes (HaCaT) and OSCC-derived cell lines (SSC9 and SCC25). Results: When the cells were stimulated with NNK, there were increases in the levels of NE secretion by HaCaT and SCC25 cells, but not by SCC9 cells. NNK (10 μM) induced cell proliferation in the HaCaT, SCC9, and SCC25 cell lines and these effects were totally inhibited by blocking β-adrenergic receptors with propranolol. The NNK-induced OSCC cell proliferation was further dependent on nicotinic acetylcholine receptors α4 (nAChR-α4) activation (totally in SCC9 cells and partially in SCC25 cells), but not dependent on nAChR-α7 activation. Inhibition of the β-adrenergic receptors, nAChR-α4 and nAChR-α7 did not block NNK-induced HaCaT proliferation. Conclusion: Our findings suggest that oral cancer cells secrete the neurotransmitter norepinephrine and the tobacco nitrosamine NNK promotes increased cell proliferation through a stress-related cellular adrenergic pathway.

Autor 1:  Ana Lívia SANTOS-SOUSA

E-mail 1:  [email protected]

Autor 2:   Flávia Alves VERZA

E-mail 2:  [email protected]

Autor 3 :  Sandra Helena Penha de OLIVEIRA

E-mail 3:  [email protected]

Autor 4:  Daniel Galera BERNABÉ

E-mail 4:  [email protected]