植物治疗方法:多环芳烃诱导细胞紊乱、自噬和凋亡的新希望

IF 2.8 4区 医学 Q2 TOXICOLOGY Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI:10.1080/15376516.2016.1268228
D. N. Das, P. Panda, P. P. Naik, Subhadip Mukhopadhyay, N. Sinha, S. Bhutia
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引用次数: 31

摘要

多环芳烃(PAHs)是一类主要的致癌化学物质,在危害人类的化学物质中排名第九。此外,对多环芳烃的兴趣主要是由于其遗传毒性、致畸性、诱变性和致癌性。细胞色素P450 (CYP450)和芳烃受体(AhR)多态性具有将原致癌物转化为致癌物的能力,是个体癌症易感性的重要因素。多环芳烃的致癌性与它们与DNA结合的能力有关,从而增强DNA交联,引起一系列破坏性作用,从而引发肿瘤。它们通过调节活性氧(ROS)的产生来诱导细胞毒性,从而仲裁细胞凋亡。此外,工业污染物多环芳烃介导的细胞毒性介导的凋亡和自噬细胞死亡以及免疫抑制为突变细胞的增殖提供了肥沃的土壤,从而导致癌症的生长和进展。多环芳烃通过促进肿瘤细胞中金属蛋白酶-9 (MMP-9)、血管内皮生长因子(VEGF)和缺氧诱导因子(HIF)的上调,在肿瘤转移所需的血管生成中发挥重要作用。本文综述了多环芳烃诱导肿瘤发生及细胞自噬和凋亡的分子机制。此外,作者还揭示了植物疗法是如何从更安全和成本效益的角度作为多环芳烃毒性作用的救世主的替代潜在疗法。
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Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death
Abstract Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their genotoxic, teratogenic, mutagenic and carcinogenic property. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) has the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development. The carcinogenicity potential of PAHs is related to their ability to bind to DNA, thereby enhances DNA cross-linking, causing a series of disruptive effects which can result in tumor initiation. They induce cellular toxicity by regulating the generation of reactive oxygen species (ROS), which arbitrate apoptosis. Additionally, cellular toxicity-mediated apoptotic and autophagic cell death and immune suppression by industrial pollutants PAH, provide fertile ground for the proliferation of mutated cells, which results in cancer growth and progression. PAHs play a foremost role in angiogenesis necessary for tumor metastasization by promoting the upregulation of metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) in human cancer cells. This review sheds light on the molecular mechanisms of PAHs induced cancer development as well as autophagic and apoptotic cell death. Besides that authors have unraveled how phytotherapeutics is an alternate potential therapeutics acting as a savior from the toxic effects of PAHs for safer and cost effective perspectives.
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来源期刊
自引率
3.10%
发文量
66
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.
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