Laboratory of Molecular and Cell Biology, Department of Life Science and Bioinformatics, Assam University, Silchar, India.
Prague Med Rep. 2020;121(4):209-235. doi: 10.14712/23362936.2020.19.
Areca nut consumption is a popular habit in Southeast Asian countries. One of the important biologically active alkaloids of areca nut is arecoline, which plays a role in mediating the development of several pathologies of the primary exposure site, the oral cavity. Studies on the metabolism of arecoline revealed the formation of several metabolites which themselves might be toxic. Moreover, polymorphisms in genes encoding enzymes involved in the metabolism of arecoline might predispose an organism towards the development of oral cancer. The present review tries to accumulate all the relevant existing literature and then elucidate the molecular mechanism by which arecoline plays a role in the development of oral submucous fibrosis and oral cancer. Existing information regarding arecoline metabolism, enzymes involved in the metabolic process and biological effects of the metabolites of arecoline have also been compiled and compared to study the toxicity of metabolites with its parent compound arecoline and whether they play any role in the pathogenesis of oral cancer mediated by areca nut consumption. A repertoire of molecular targets has come up in the discussion whose expression profile is perturbed by arecoline. Construction of induction cascade from existing literature has given an idea about the process of molecular pathogenesis. The summarized and analysed data can help to determine the molecular mechanism and drug targets, which in turn could be helpful in the prevention or treatment of these pathological conditions. It also brings into light areas where further research needs to be directed.
槟榔果的食用在东南亚国家是一种流行的习惯。槟榔果中一种重要的生物活性生物碱是槟榔碱,它在介导口腔这一初级暴露部位的几种病理学的发展中发挥作用。对槟榔碱代谢的研究揭示了几种代谢物的形成,而这些代谢物本身可能是有毒的。此外,编码槟榔碱代谢相关酶的基因中的多态性可能使机体易患口腔癌。本综述试图收集所有相关的现有文献,然后阐明槟榔碱在口腔黏膜下纤维性变和口腔癌发展中的作用的分子机制。还编译并比较了有关槟榔碱代谢、代谢过程中涉及的酶以及槟榔碱代谢物的生物学效应的现有信息,以研究代谢物与其母体化合物槟榔碱的毒性以及它们是否在槟榔果食用介导的口腔癌发病机制中发挥作用。在讨论中出现了一系列分子靶标,其表达谱受槟榔碱的影响。根据现有文献构建诱导级联反应,为分子发病机制的研究提供了思路。总结和分析的数据有助于确定分子机制和药物靶点,这反过来又有助于预防或治疗这些病理状况。它还揭示了需要进一步研究的领域。