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

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.

Keywords: Cancer targets; EGFR; FGFR; PDGFR; VEGFR; abnormal signal transduction; natural inhibitors..