The 13th World Conference on Tobacco OR Health

Objective: Objective of this study is to study the role of the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in lung cancer cell death.

Methods: NCI-H23, a non-small lung cell carcinoma cell line, and CRL-2066, a small lung cell carcinoma line were used in the experiment. Cell death was determined by MTT assay. The effect of NNK on a cell survival factor, nuclear factor kappa B, was analyzed by Western blot and electrophoretic mobility shift assay (EMSA) and confocal microscopy.

Results: Staurosporine could significantly induced cell death of both NCI-H23 cells and CRL-2066 cells. Both types of cells treated by NNK showed a significant resistance to the cell death induced by staurosporine. Western blot indicated that p65, a subunit of nuclear factor kappa B, was induced by NNK at a time-dependent manner. NNK also showed to significantly activate nuclear factor kappa B, evident by a marked increase in phospho IkB-? protein, which allows translocation of nuclear factor kappa B from the cytoplasm to the nucleus. Using a confocal microscopy, we confirmed the occurrence of such a translocation of nuclear factor kappa B in lung cancer cells treated by NNK. The change in nuclear factor kappa B collaborated with resistance of the cells to the cell death stimulation at the presence of NNK.

Conclusion: NNK can prevent lung cancer cells from cell death induced by staurosporine. The activation of the cellular survival factor, nuclear factor kappa B, by NNK may be, at least in part, responsible for the effect of NNK on lung cancer cells observed.