Novel Pathways and Mechanisms of Nicotine-Induced Oral Carcinogenesis.

IF 2.5 4区医学 Q3 ONCOLOGY

Recent patents on anti-cancer drug discovery Pub Date : 2022-01-01 DOI:10.2174/1574892816666210806161312

Mohit Sharma, Smitha S Shetty, Raghu A Radhakrishnan

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引用次数: 5

Abstract

Background: Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine- derived Nitrosamines (NDNs).

Methods: A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis.

Results: Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade, promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR.

Conclusion: Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.

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尼古丁诱导口腔癌变的新途径和机制。

背景:无烟烟草(SLT)的尼古丁含量是吸烟烟草(SMT)的9倍。尼古丁的致癌作用通过将尼古丁转化为尼古丁衍生的亚硝胺(NDNs)而增强。方法:对相关文献进行回顾，并采用量身定制的搜索策略来揭示尼古丁诱导的口腔癌变的新途径和机制。结果:尼古丁和ndn作为激动剂作用于烟碱乙酰胆碱受体(nAChRs)。尼古丁通过α4β2nAChR和α7nAChR促进渴望，通过增强大脑多巴胺释放。尼古丁结合nAChR促进口腔癌细胞的增殖、迁移、侵袭、化疗耐药、放射耐药和转移。尼古丁结合角化细胞α7nAChR触发Ras/Raf-1/MEK1/ERK级联，促进抗凋亡和促增殖作用。此外，尼古丁增强的转移通过减少p-EGFR的核定位而受到nAChR阻断的抑制。结论:长期暴露于尼古丁/NDN可增强促癌性α7nAChR，使抑癌性α4β2nAChR脱敏。既然nachr决定了尼古丁的成瘾性和致癌性，把尼古丁仅仅作为一种没有任何致癌性的成瘾性似乎是违反直觉的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Recent patents on anti-cancer drug discovery 医学-药学

CiteScore

4.50

自引率

7.10%

发文量

审稿时长

3 months

期刊介绍： Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.