Pomegranate Phytoconstituents Blunt The Inflammatory Cascade In A Chemically Induced Rodent Model Of Hepatocellular Carcinogenesis
Biochemistry & Molecular Biology; cancer chemoprevention; chemoprevention; cyclooxygenase-2; cyclooxygenase-2; factor-kappa-b; gene-expression; heat-shock proteins; hepatocarcinogenesis; human-disease; inflammation; inhibitors; molecular chaperones; nitric-oxide synthase; Nuclear factor-kappaB; Nutrition & Dietetics; oxidative stress; Pomegranate; punica-granatum l.
Bishayee A; Thoppil R J; Darvesh A S; Ohanyan V; Meszaros J G; Bhatia D
Journal of Nutritional Biochemistry
2013
2013-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.jnutbio.2012.04.009" target="_blank" rel="noreferrer noopener">10.1016/j.jnutbio.2012.04.009</a>
Black Currant Phytoconstituents Exert Chemoprevention Of Diethylnitrosamine-initiated Hepatocarcinogenesis By Suppression Of The Inflammatory Response
Biochemistry & Molecular Biology; cancer-cell proliferation; chemoprevention; cyclooxygenase-2; cyclooxygenase-2 inhibitors; gamma-glutamyl-transferase; heat-shock proteins; heat-shock proteins; hepatocarcinogenesis; human hepatocellular-carcinoma; inflammation; liver cancer; molecular chaperones; nf-kappa-b; nuclear factor-B; Oncology; ribes-nigrum; signaling; united-states
Bishayee A; Thoppil R J; Mandal A; Darvesh A S; Ohanyan V; Meszaros J G; Haznagy-Radnai E; Hohmann J; Bhatia D
Molecular Carcinogenesis
2013
2013-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/mc.21860" target="_blank" rel="noreferrer noopener">10.1002/mc.21860</a>
Pomegranate Phytoconstituents Blunt The Inflammatory Cascade In A Chemically Induced Rodent Model Of Hepatocellular Carcinogenesis
Biochemistry & Molecular Biology; cancer chemoprevention; Chemoprevention; cyclooxygenase-2; cyclooxygenase-2; factor-kappa-b; gene-expression; heat-shock proteins; hepatocarcinogenesis; human-disease; Inflammation; inhibitors; molecular chaperones; nitric-oxide synthase; Nuclear factor-kappaB; Nutrition & Dietetics; oxidative stress; Pomegranate; punica-granatum l.
Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. Due to dismal prognosis and limited therapeutic intervention, chemoprevention has emerged as a viable approach to reduce the morbidity and mortality of HCC. Pomegranate fruit is a rich source of phytochemicals endowed with potent antioxidant and anti-inflammatory properties. We previously reported that pomegranate phytochemicals inhibit diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats though nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant mechanisms. Since Nrf2 also acts as a key mediator of the nuclear factor-kappaB (NF-kappa B)-regulated inflammatory pathway, our present study investigated the anti-inflammatory mechanisms of a pomegranate emulsion (PE) during DENA-induced rat hepatocarcinogenesis. Rats were administered with PE (1 or 10 g/kg) 4 weeks before and 18 weeks following DENA initiation. There was a significant increase in hepatic expressions of inducible nitric oxide synthase, 3-nitrotyrosine, heat shock protein 70 and 90, cyclooxygenase-2 and NF-kappa B in DENA-exposed rat livers. PE dose-dependently suppressed all aforementioned elevated inflammatory markers. A conspicuous finding of this study involves lack of cardiotoxicity of PE as assessed by monitoring cardiac function using noninvasive echocardiography. Our results provide substantial evidence that suppression of the inflammatory cascade through modulation of NF-kappa B signaling pathway may represent a novel mechanism of liver tumor inhibitory effects of PE against experimental hepatocarcinogenesis. Data presented here coupled with those of our earlier study underline the importance of simultaneously targeting two interconnected molecular circuits, namely, Nrf2-mediated redox signaling and NF-kappa B-regulated inflammatory pathway, by pomegranate phytoconstituents to achieve chemoprevention of HCC. (C) 2013 Elsevier Inc. All rights reserved.
Bishayee A; Thoppil R J; Darvesh A S; Ohanyan V; Meszaros J G; Bhatia D
Journal of Nutritional Biochemistry
2013
2013-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.jnutbio.2012.04.009" target="_blank" rel="noreferrer noopener">10.1016/j.jnutbio.2012.04.009</a>
Black Currant Phytoconstituents Exert Chemoprevention Of Diethylnitrosamine-initiated Hepatocarcinogenesis By Suppression Of The Inflammatory Response
Biochemistry & Molecular Biology; cancer-cell proliferation; Chemoprevention; cyclooxygenase-2; cyclooxygenase-2 inhibitors; gamma-glutamyl-transferase; heat-shock proteins; heat-shock proteins; hepatocarcinogenesis; human hepatocellular-carcinoma; Inflammation; liver cancer; molecular chaperones; nf-kappa-b; nuclear factor-B; Oncology; ribes-nigrum; signaling; united-states
Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500mg/kg) treatment for 22wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-B (NF-B) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-B signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer. (c) 2011 Wiley Periodicals, Inc.
Bishayee A; Thoppil R J; Mandal A; Darvesh A S; Ohanyan V; Meszaros J G; Haznagy-Radnai E; Hohmann J; Bhatia D
Molecular Carcinogenesis
2013
2013-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/mc.21860" target="_blank" rel="noreferrer noopener">10.1002/mc.21860</a>