Polyphenol compounds and PKC signaling

Abstract

Background Naturally occurring polyphenols found in food sources provide huge health benefits. Several polyphenolic compounds are implicated in the prevention of disease states, such as cancer. One of the mechanisms by which polyphenols exert their biological actions is by interfering in the protein kinase C (PKC) signaling pathways. PKC belongs to a superfamily of serine-threonine kinase and are primarily involved in phosphorylation of target proteins controlling activation and inhibition of many cellular processes directly or indirectly. Scope of review Despite the availability of substantial literature data on polyphenols' regulation of PKC, no comprehensive review article is currently available on this subject. This article reviews PKC-polyphenol interactions and its relevance to various disease states. In particular, salient features of polyphenols, PKC, interactions of naturally occurring polyphenols with PKC, and future perspective of research on this subject are discussed. Major conclusions Some polyphenols exert their antioxidant properties by regulating the transcription of the antioxidant enzyme genes through PKC signaling. Regulation of PKC by polyphenols is isoform dependent. The activation or inhibition of PKC by polyphenols has been found to be dependent on the presence of membrane, Ca2+ ion, cofactors, cell and tissue types etc. Two polyphenols, curcumin and resveratrol are in clinical trials for the treatment of colon cancer. General significance The fact that 74% of the cancer drugs are derived from natural sources, naturally occurring polyphenols or its simple analogs with improved bioavailability may have the potential to be cancer drugs in the future.

The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats

“…25 Phosphorylation of Nrf2 allows the Nrf2 to translocate to the nucleus and bind to the antioxidant response element in the regulatory region of the target genes and induces the transcription of antioxidant enzymes. 26 Pre-clinical studies have shown that orally delivered curcumin has neuroprotective effects 27 and has been found to reduce lipid peroxidation by maintaining the activities of antioxidant enzymes such as CAT, SOD, GPx, and GSH levels in rats exposed with neurotoxic compounds. 28,29 The ability of curcumin to increase the GSH levels is due to its affinity to induce the transcription of the mRNAs for the GSH biosynthetic genes.…”

Ahr-bacterial diet interaction modulates aging and associated pathologies inC. elegans

“…ROS reduction) remain to be clarified but our preliminary in silico analysis suggests that it is unlikely through a direct binding of curcumin to the AHR-1 ligand binding domain. Accordingly, while direct ligandbinding has not been verified for many of the polyphenolic AhR modulators, ligandindependent effects on AhR signaling, like binding to HSP90 (Palermo, Westlake et al, 2005) or inhibition of AhR phosphorylation by the protein kinase C (Das, Ramani et al, 2016, Nishiumi et al, 2007 , have been instead described.…”

Curcumin Inhibits Protein Kinase Cα Activity by Binding to Its C1 Domain

“…To further determine the relative affinity of curcumin for the αC1A and αC1B sub-domains, we studied their interactions with curcumin using a fluorescence assay previously used to study the effect of resveratrol with PKC (55). Resveratrol is another naturally occurring polyphenol known for its interaction with PKC (56). Our results show that phorbol 13-acetate displaced curcumin from αC1A and αC1B with IC 50 values of 6.27± 1.2 μM and 4.47±1.7 μM, respectively, indicating slightly higher affinity of the αC1B than αC1A.…”