Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

Flora, Silvio De; Izzotti, Alberto; Albini, Adriana; D’Agostini, Francesco; Bagnasco, Maria; Balansky, Roumen

doi:10.1007/978-1-59259-767-3_3

Cited by 16 publications

(15 citation statements)

References 307 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, budesonide and NAC exerted a variety of protective effects on preneoplastic and neoplastic alterations induced by B[a]P. The protective effect of budesonide is consistent with the well known antiinflammatory properties of glucocorticoids (14). Among the variety of mechanisms of NAC, this thiol compound has antiinflammatory properties and inhibits triggering of apoptosis consequent to DNA damage and redox imbalances (22). NAC has been shown to prevent alopecia induced by either doxorubicin (28) or cigarette smoke (29) in C57BL͞6 mice or by 2-chloroethyl ethyl sulfide in guinea pigs (35).…”

Section: Discussionsupporting

confidence: 66%

“…The safety of this drug in humans is supported by Ͼ40 years of clinical use, mainly as a mucolytic agent but also as an antidote against acute intoxication (21,22). A number of experimental studies in animal models performed during the last 20 years and phase II clinical trials, along with mechanistic considerations, provide evidence for the potential ability of this thiol compound to inhibit oxidative, genotoxic, and carcinogenic effects (reviewed in refs.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Influence of FHIT on benzo[ a ]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N -acetylcysteine

Balansky

D’Agostini

Ganchev³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 99%

Influence of FHIT on benzo[ a ]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N -acetylcysteine

Balansky

D’Agostini

Ganchev³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…N-acetylcysteine is an analogue and precursor of L-cysteine and reduced glutathione, which has been shown to exert a variety of protective effects and mechanisms in mutagenesis and carcinogenesis (39,40). Interestingly, in the same rats used in the present study, N-acetylcysteine and its combination with oltipraz were the only treatments capable of significantly decreasing the frequency of apoptotic cells in the bronchial/bronchiolar epithelium.…”

Section: Discussionmentioning

confidence: 57%

Early Loss of Fhit in the Respiratory Tract of Rodents Exposed to Environmental Cigarette Smoke

D’Agostini

Izzotti

Balansky³

et al. 2006

Cancer Research

Self Cite

View full text Add to dashboard Cite

The Fhit gene, encompassing the most active common human chromosomal fragile region, FRA3B, has been shown to act as a tumor suppressor. Several studies have shown significant Fhit alterations or Fhit protein loss in lung cancers from smokers compared with lung cancers from nonsmokers. To evaluate the role of Fhit under controlled experimental conditions, we exposed rodents to environmental cigarette smoke (ECS) and evaluated Fhit expression or Fhit protein in the respiratory tract. After 14 days of exposure to ECS, loss of Fhit protein in the bronchial/bronchiolar epithelium affected half of the tested B6-129(F 1 ) mice, either wild type or Fhit +/À . After 28 days, it affected the vast majority of the tested SKH-1 hairless mice and of A/J mice and all (UL53-3 x A/J)F 1 mice, either wild type or P53 +/À . In Sprague-Dawley rats, exposure to ECS for up to 30 days caused a time-dependent loss of Fhit in pulmonary alveolar macrophages. Moreover, ECS downregulated Fhit expression and significantly decreased Fhit protein in the rat bronchial epithelium. The oral administration of N-acetylcysteine attenuated the ECS-related loss of Fhit, whereas oltipraz, 5,6-benzoflavone, phenethyl isothiocyanate, and indole 3-carbinol, and their combinations had no significant effect. Parallel studies evaluated a variety of molecular, biochemical, and cytogenetic alterations in the respiratory tract of the same animals. In conclusion, there is unequivocal evidence that Fhit is an early, critical target in smoke-related lung carcinogenesis in rodents, and that certain chemopreventive agents can attenuate the occurrence of this gene alteration. (Cancer Res 2006; 66(7): 3936-41)

show abstract

“…The most effectively modulated miRNAs in ECS-exposed rats treated with NAC, an analogue and precursor of reduced glutathione, are involved in NF-κB–mediated stress response ( miR-146-prec ) and P53 functions ( miR-34b, miR-34c , and miR-140s ). NAC, besides being a potent scavenger of free radicals, works through multiple mechanisms, also including its ability to inhibit activation and nuclear translocation of NF-κB, to modulate the post-translational increase of P53 expression, and to decrease TGF-β biological activity (30, 31). In particular, attenuation by NAC of ECS-induced miRNA downregulation is consistent with the observed attenuation of ECS-induced proteins or functions in rodent lung.…”

Section: Discussionmentioning

confidence: 99%

Chemoprevention of Cigarette Smoke–Induced Alterations of MicroRNA Expression in Rat Lungs

Izzotti

Calin

Steele

et al. 2010

Cancer Prevention Research

Self Cite

106

100

View full text Add to dashboard Cite

We previously showed that exposure to environmental cigarette smoke (ECS) for 28 days causes extensive downregulation of microRNA expression in the lungs of rats, resulting in the overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lungs of either ECS-free or ECS-exposed rats treated with the orally administered chemopreventive agents N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone, and phenethyl isothiocyanate (as single agents or in combinations). This is the first study of microRNA modulation by chemopreventive agents in nonmalignant tissues. Scatterplot, hierarchical cluster, and principal component analyses of microarray and quantitative PCR data showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, indicating potential safety. On the other hand, all of them attenuated ECS-induced alterations but to a variable extent and with different patterns, indicating potential preventive efficacy. The main ECS-altered functions that were modulated by chemopreventive agents included cell proliferation, apoptosis, differentiation, Ras activation, P53 functions, NF-κB pathway, transforming growth factor–related stress response, and angiogenesis. Some micro-RNAs known to be polymorphic in humans were downregulated by ECS and were protected by chemopreventive agents. This study provides proof-of-concept and validation of technology that we are further refining to screen and prioritize potential agents for continued development and to help elucidate their biological effects and mechanisms. Therefore, microRNA analysis may provide a new tool for predicting at early carcinogenesis stages both the potential safety and efficacy of cancer chemopreventive agents.

show abstract

Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

Cited by 16 publications

References 307 publications

Influence of FHIT on benzo[ a ]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N -acetylcysteine

Influence of FHIT on benzo[ a ]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N -acetylcysteine

Early Loss of Fhit in the Respiratory Tract of Rodents Exposed to Environmental Cigarette Smoke

Chemoprevention of Cigarette Smoke–Induced Alterations of MicroRNA Expression in Rat Lungs

Contact Info

Product

Resources

About