The Role of the MAPK Signaling, Topoisomerase and Dietary Bioactives in Controlling Cancer Incidence

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.

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

“…Various intracellular upstream signaling cascades, particularly the mitogen activated protein kinase (MAPK) pathways, regulate the production of MMP-2 and MMP-9. The major components of the MAPK pathways, the ERK, JNK, and p38 MAPK pathways, regulate cell migration, invasion, proliferation, survival, and apoptosis following different cellular signals [17, 18]. α-mangostin can modulate tumor migration and invasion by down-regulating MMP-2, MMP-9, and urokinase-type plasminogen activator (µPA) through the αvβ3 integrin receptor and the FAK/ERK/NF-κB signal pathway in lung cancer [19], by downregulating the JNK-mediated pathway and inhibition of NK-κB and AP-1 binding activity in prostate cancer [20], and by suppressing the ERK-mediated pathway and reducing AP-1 and NK-κB binding in breast cancer [21].…”

Identification of Functional MKK3/6 and MEK1/2 Homologs from Echinococcus granulosus and Investigation of Protoscolecidal Activity of Mitogen-Activated Protein Kinase Signaling Pathway Inhibitors In Vitro and In Vivo

“…MEK1/2/5 specifically recognizes Erk-like MAPKs, harboring a T-E-Y motif in the activation loop, while MKK3/6as well as MKK4/7-like MAPKKs are specific for p38 (T-G-Y) and JNK-like (T-P-Y) MAPKs, respectively (15,16). Recent evidence indicates that therapies targeted toward MAPK pathway components stand out as potential alternative drugs in many tumor types (17)(18)(19).…”

Berberine inhibits the interleukin‐1 beta‐induced inflammatory response via MAPK downregulation in rat articular chondrocytes

“…The MAPK signaling pathway (p38, ERK, and JNK) is involved in various cellular biological activities, such as cell proliferation, survival, and differentiation (Selim, Abdelrasoul, Aboelmagd, & Tawila, ). Previous studies showed that inhibition of the production of iNOS, COX‐2, and MMPs acted through the MAPK signaling pathway (Chen et al, ; Ma et al, ).…”