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天然来源的 EGFR、PDGFR、FGFR 和 VEGFR 介导的信号通路抑制剂作为潜在的抗癌药物。

Natural Sourced Inhibitors of EGFR, PDGFR, FGFR and VEGFRMediated Signaling Pathways as Potential Anticancer Agents.

机构信息

Global Institute of Pharmaceutical Education and Research, Kashipur-244713,India.

Cytogenetics and Molecular Biology Lab., Department of Zoology, University of Kalyani, Kalyani-741235,India.

出版信息

Curr Med Chem. 2022;29(2):212-234. doi: 10.2174/0929867328666210303101345.

Abstract

The molecular mechanisms of mitotic cell cycle progression involve very tightly restricted types of machinery which are highly regulated by a fine balance between the positive and negative accelerators (or regulators). These regulators include several checkpoints that have proteins acting as enzymes and their activating partners. These checkpoints incessantly monitor the external as well as internal environments such as growth signals, favorable conditions for growth, cell size, DNA integrity of the cell and hence function to maintain the highly ordered cell cycle progression by sustaining cell homeostasis and promoting error-free DNA replication and cell cycle division. To progress through the mitotic cell cycle, the cell has to successfully drive past the cell cycle checkpoints. Due to the abnormal behavior of some cell cycle proteins, the cells tend to divide continuously overcoming the tight regulation of cell cycle checkpoints. Such anomalies may lead to unwanted cell division, and this deregulation of cell cycle events is considered as one of the main reasons behind tumor development, and thus, cancer progression. So the understanding of the molecular mechanisms in cancer progression might be insightful for designing several cancer treatment strategies. The deregulation in the checkpoints is caused due to the changes in the tyrosine residues of TPKs via PDGFR, EGFR, FGFR, and VEGFR-mediated signaling pathways. Therefore, the inhibitors of PDGFR, EGFR, FGFR, and VEGFR-mediated signaling pathways could be potential anticancer agents. The resistance and toxicity in the existing synthetic anticancer chemotherapeutics may decrease the life span of a patient. For long, natural products have played an essential alternative source of therapeutic agents due to having least or no side effect and toxicity. The present study is an attempt to promote natural anticancer drug development focusing on the updated structural information of PDGFR, EGFR, FGFR, and VEGFR inhibitors isolated from the plant sources. The data used in this review has been collected from internet resources, viz. GOOGLE Web, GOOGLE SCHOLAR, and PubMed Central. The citation of each report was first checked, after which the articles were selected as an authentic reference for the present study. Around 200 journal articles were initially selected, of which around 142 were finally chosen for presenting the study on the natural sourced inhibitors of EGFR, PDGFR, FGFR, and VEGFR-mediated signaling pathways which may help to enhance the potential cancer treatment.

摘要

有丝分裂细胞周期进展的分子机制涉及非常严格限制的机制类型,这些机制受到正负加速器(或调节剂)之间精细平衡的高度调节。这些调节剂包括几种检查点,其中有作为酶的蛋白质及其激活伙伴。这些检查点不断监测外部和内部环境,例如生长信号、有利于生长的条件、细胞大小、细胞的 DNA 完整性,因此通过维持细胞内稳态和促进无差错的 DNA 复制和细胞周期分裂来维持高度有序的细胞周期进展。为了通过有丝分裂细胞周期,细胞必须成功地通过细胞周期检查点。由于一些细胞周期蛋白的异常行为,细胞往往会连续分裂,克服细胞周期检查点的严格调节。这种异常可能导致不必要的细胞分裂,并且这种细胞周期事件的失调被认为是肿瘤发展背后的主要原因之一,因此是癌症进展的原因之一。因此,了解癌症进展中的分子机制可能有助于设计几种癌症治疗策略。检查点的失调是由于 TPKs 的酪氨酸残基通过 PDGFR、EGFR、FGFR 和 VEGFR 介导的信号通路发生变化而引起的。因此,PDGFR、EGFR、FGFR 和 VEGFR 介导的信号通路抑制剂可能是潜在的抗癌剂。现有合成抗癌化疗药物的耐药性和毒性可能会降低患者的寿命。长期以来,由于副作用和毒性最小或没有,天然产物一直是治疗剂的重要替代来源。本研究旨在促进天然抗癌药物的开发,重点是从植物来源中分离出的 PDGFR、EGFR、FGFR 和 VEGFR 抑制剂的最新结构信息。本综述中使用的数据是从互联网资源(即 GOOGLE Web、GOOGLE SCHOLAR 和 PubMed Central)收集的。首先检查了每个报告的引文,然后选择这些文章作为本研究的可靠参考。最初选择了大约 200 篇期刊文章,其中最终选择了大约 142 篇文章来介绍 EGFR、PDGFR、FGFR 和 VEGFR 介导的信号通路天然来源抑制剂的研究,这可能有助于提高潜在的癌症治疗效果。

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