Evidence for the role of nitric oxide in antiapoptotic and genotoxic effect of nicotine on human gingival fibroblasts

Abstract

Resistance to apoptosis is essential for cancer survival and plays a critical role in carcinogenesis. Growing evidence suggests that nicotine can act as a tumor promoter, impairing apoptotic process in certain types of human cancer cell lines. Our previous study revealed in human gingival fibroblasts (HGFs) a concomitant antiapoptotic and genotoxic effect of nicotine, manifested by the attenuation of staurosporine (STP)-induced apoptosis and the increase of micronucleus frequency. The present report provides evidence that nitric oxide (NO) is critically involved in these actions. In vitro treatment with sodium nitroprusside as NO donor showed that NO produced similar effects as those observed with nicotine: it caused DNA damage and partially prevented apoptosis induced by staurosporine. Exposure of HGFs to nicotine, at concentrations similar to those found in the blood of habitual smokers, leads to the production of NO associated with the induction of inducible nitric oxide synthase (iNOS) expression. Experiments using an inhibitor of iNOS, N-monomethyl-L-arginine (NMA), together with nicotine confirmed the involvement of NO in the drug action, abrogating completely cell death and a good part of the genotoxicity. Finally, we show by different approaches that the inhibition of cell death by nicotine through NO release is related to modulation of caspase-1 activation.

Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract

“…Considering the fact that almost half of EC liquids content we examined was propylene glycol, the results of our study indicate that it is unlikely for propylene glycol to be pyrolyzed to acetaldehyde by EC use or to have any significant cytotoxic effect by itself. Concerning nicotine, there are studies showing that, at levels commonly found in cigarettes, it does not induce cell death (Laytragoon-Lewin et al, 2011) and may even have anti-apoptotic effects (Argentin & Cicchetti, 2006, 2004. It should be mentioned, however, that these effects have been suggested to facilitate the growth of tumors already initiated (Davis et al, 2009).…”

Nicotine and apoptosis

“…In contrast, higher concentrations of nicotine (10 lM-1 mM) caused an increase in micronuclei and significantly (p = 0.005) reduced cell survival. Furthermore, they found that 1 lM nicotine significantly attenuated staurosporine-induced apoptosis [49,50].…”

Cardiac-specific overexpression of metallothionein rescues nicotine-induced cardiac contractile dysfunction and interstitial fibrosis

“…A growing body of evidence has consolidated that notion that cigarette smoking unfavorably affects the structure and function of cardiovascular system (Goette et al , 2007; Zhou et al , 2010). As one of the major toxins in cigarette smoke and smokeless tobacco, nicotine contributes to severe oxidative stress and oxidative damage in various organs and tissues from humans (Argentin and Cicchetti, 2004; Argentin and Cicchetti, 2006). Consistently, experimental evidence in rodents also confirmed the development of oxidative tissue injury following chronic nicotine administration (Ceconi et al , 2003; Miyauchi et al , 2005).…”