Abstract

Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities.

Highlights

  • Reactive oxygen species (ROS) are known to be involved in a wide range of human diseases, including cancer

  • The oxidative damage that ROS cause can lead to DNA mutations which result in Diseases 2017, 5, 13; doi:10.3390/diseases5020013

  • (MAPKs) are cell a family serine/threonine protein kinases, which implicated in multiple cellular functions, ranging from cellSuch survival andphosphorylation proliferation, to cell phosphorylate their substrates at serine and/or residues

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Summary

Introduction

Reactive oxygen species (ROS) are known to be involved in a wide range of human diseases, including cancer. They levels of ROS regulate normal cell proliferation as well cell signaling [1] They act as a act as a secondary messenger molecules. Oxidative stress can have an effect on the signaling pathways of redoxe.g., Src, kinases, PI3K-Akt andSrc, MAPK (Erk, JNK, p38). These regulate several transcription factors sensitive e.g., PI3K-Akt and MAPK Activation of such pathways can induce transcription factors through the phosphorylation of their protein modules Activation of such proliferation cellular transformation [1,4]

ROS and Cell Signaling
ROS Activate MAPK Pathway
Topoisomerase
Classification of Topoisomerases
Topoisomerase Inhibition
Pterocarpans
Results
Conclusions
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