Chemopreventive and hepatoprotective effects of genistein via inhibition of oxidative stress and the versican/PDGF/PKC signaling pathway in experimentally induced hepatocellular carcinoma in rats by thioacetamide

Abstract

Objective Genistein is a recognized isoflavone present in soybeans with antioxidant, anti-inflammatory, antiangiogenic and antitumor activities. This study aimed to test ability of genistein in modulating versican/platelet derived growth factor (PDGF) axis in HCC. Methods HCC was experimentally induced in male Sprague-Dawley rats then treated with 25 or 75 mg/kg genistein. Antioxidant activities of genistein was assessed by measuring the gene expression of Nrf2 and the hepatic levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione. Expression of versican, PDGF, protein kinase C (PKC) and ERK-1 protein was assessed by Western blotting and immunostaining. Results HCC induced an elevation in oxidative stress, PDGF, versican, PKC and ERK protein expression levels. Genistein significantly reduced an HCC-induced increase in oxidative stress. Moreover, genistein dose-dependently reduced HCC-induced elevation of PDGF, versican, PKC and ERK protein expression levels. Moreover, genistein helped retain a normal hepatocyte structure and reduced fibrous tissue deposition, especially in high dose. Conclusions Genistein exerted antitumor and antioxidant effects and therefore suppress HCC development via inhibition of the PDGF/versican bidirectional axis, suppressing both ERK1 and PKC as downstream regulators. Therefore, genistein is a potential novel therapeutic candidate for improving the outcome of patients with HCC.

Metabolomic analysis reveals dynamic changes in secondary metabolites of Sophora japonica L. during flower maturation

“…Most of these components have positive therapeutic effects on cardiovascular and hepatic diseases. For example, genistein ( El-Far et al, 2022 ), epigallocatechin gallate ( George et al, 2022 ), pinocembrin ( Cao et al, 2022 ), and p-coumaric acid ( Bal et al, 2022 ) of Flos Sophorae Immaturus are effective in treating liver-related diseases, clearing the liver, and ameliorating hepatic fire. Genistin ( Gu et al, 2016 ), catechin ( Rodriguez et al, 2006 ), and cinnamic acid ( Luan et al, 2022 ) complement the treatment of cardiovascular diseases by cooling the blood and inhibiting hemorrhage.…”

SCARB1‐encoded circ _0029343 induces p73 splicing to promote growth and metastasis of hepatocellular carcinoma via miR‐486‐5p/SRSF3 axis

“…[22] PDGF expression is also closely associated with HCC grade and invasion, indicating the critical effect of PDGF on the progression and metastasis of HCC. [40] A prior study has also suggested that p73 could regulate cell cycle arrest and apoptosis, and increased ΔNp63 and ΔNp73 expression are correlated with tumor recurrence and reduced survival, [41] suggesting that overexpressed SRSF3 enhanced the SRSF3 (Figure 8). It is hoped that studying the circ _0029343mediating miR-486-5p/SRSF3 axis mechanism will stimulate a greater interest in prospective studies, and these will lead to the discovery of novel and effective therapeutic targets for HCC treatment.…”

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences

“…This should be combined with the use of better infection models representing the three-dimensional architecture of the liver, the heterogeneity of its cell populations, and the contribution of immune cells. Signaling pathways are established targets in cancer therapy [ 177 ] and have previously drawn attention as targets for cancer prevention attenuating liver disease progression [ 178 , 179 ]. Host signaling-targeting approaches to battle chronic infection have been discussed [ 133 , 180 , 181 ] as they hold the potential to lower the genetic barrier of resistance to direct-acting antivirals.…”