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癌症进展中的上皮-间质转化:预防性植物化学物质

Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals.

作者信息

Illam Soorya P, Narayanankutty Arunaksharan, Mathew Shaji E, Valsalakumari Remya, Jacob Rosemol M, Raghavamenon Achuthan C

机构信息

Department of Biochemistry, Amala Cancer Research Centre, Amala Nagar P.O. Thrissur, Kerala- 680555. India.

Department of Biochemistry, Amala Cancer Research Centre, Amala Nagar P.O. Thrissur- 680 555, Kerala. India.

出版信息

Recent Pat Anticancer Drug Discov. 2017;12(3):234-246. doi: 10.2174/1574892812666170424150407.

Abstract

BACKGROUND

Epithelial-Mesenchymal Transition (EMT) is the conversion of epithelial cells into mesenchymal phenotype generally observed during embryogenesis and wound healing as well as in malignant transformation. Several signaling pathways and transcription factors associated with EMT have been explored. Dietary phytochemicals that are multi-targeted agents which interfere with these pathways, assume preventive potential against pathologic EMT.

OBJECTIVE

The present review aims to provide a detailed description of the nature and characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention.

METHOD

Details regarding the initiation, progression as well as prevention of pathologic EMT and metastasis and recent patents on preventive phytochemicals were obtained from PubMed literatures and patent databases.

RESULTS

The phenotypic changes during EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which are activated through diverse signaling pathways of TGF-β, NF-kB, Wnt and Notch. s phytocompounds that are potent enough to interfere with these signaling pathways, which in turn prevent pathological implications of EMT. Present review also discusses 28 recent patents on those phytocompounds.

CONCLUSION

EMT is a significant pharmacological target for developing preventive agents to combat pathological conditions like malignancy. Many of the phytochemicals cited in this review are being enrolled for different phases of clinical trials for their efficacy. In spite of the major limitations regarding bioavailability, sensitivity and tolerance of these compounds, their synthetic analogs, formulations and efficient drug delivery systems are also being attempted which will hopefully generate productive and promising results in near future.

摘要

背景

上皮-间质转化(EMT)是上皮细胞向间充质表型的转变,通常发生在胚胎发育、伤口愈合以及恶性转化过程中。人们已经探索了几种与EMT相关的信号通路和转录因子。具有多靶点作用且能干扰这些通路的膳食植物化学物质具有预防病理性EMT的潜力。

目的

本综述旨在详细描述生理和病理生理条件下EMT的性质和特征,以及植物化学物质在预防EMT方面的作用范围。

方法

从PubMed文献和专利数据库中获取有关病理性EMT的起始、进展、预防以及转移的详细信息,以及关于预防性植物化学物质的最新专利。

结果

EMT过程中的表型变化由Snail、Slug、Twist和Zeb等转录因子调控,这些转录因子通过TGF-β、NF-κB、Wnt和Notch等多种信号通路被激活。植物化合物能够有效干扰这些信号通路,进而预防EMT的病理影响。本综述还讨论了关于这些植物化合物的28项最新专利。

结论

EMT是开发预防恶性肿瘤等病理状况的预防药物的重要药理学靶点。本综述中引用的许多植物化学物质因其疗效正在进行不同阶段的临床试验。尽管这些化合物在生物利用度、敏感性和耐受性方面存在主要限制,但人们也在尝试其合成类似物、制剂和高效药物递送系统,有望在不久的将来产生有成效且有前景的结果。

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