1. Hepatoprotective effect of hesperidin in hepatocellular carcinoma: Involvement of Wnt signaling pathways.
- Author
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Zaghloul RA, Elsherbiny NM, Kenawy HI, El-Karef A, Eissa LA, and El-Shishtawy MM
- Subjects
- Animals, Gene Expression Regulation drug effects, Male, Rats, Rats, Sprague-Dawley, Thioacetamide toxicity, Wnt-5a Protein metabolism, Wnt3A Protein metabolism, Carcinoma, Hepatocellular prevention & control, Hesperidin pharmacology, Liver Neoplasms prevention & control, Oxidative Stress drug effects, Wnt Signaling Pathway drug effects
- Abstract
Aims: Wnt3a and Wnt5a are ligands orchestrating the canonical and non-canonical pathways, respectively, with involvement in hepatocellular carcinoma (HCC). Hesperidin (HP) is a natural product found in citrus fruits and reputed for its antitumor activity. The present study aims to investigate the potential hepatoprotective effect of HP against thioacetamide (TAA)-induced HCC focusing on its potential role on Wnt3a and Wnt5a signaling pathways., Main Methods: Forty rats were equally divided into groups; normal control, HP control (receiving HP, 150mg/kg/day), HCC (receiving TAA, 200mg/kg twice weekly for 14weeks) and HP-HCC (receiving HP and TAA). Gene expressions of Wnt3a, Wnt5a, β-catenin and Cyclin D1 were assessed by qPCR, while their protein levels, along with active caspase-3 level, were quantified by ELISA and immunohistochemistry. Liver functions, oxidative stress parameters and myeloperoxidase activity were measured. MTT assay of hepG2 cells treated with recombinant Wnt3a (10ng/ml) in presence or absence of HP (100μM) was performed., Key Findings: HCC group exhibited a significant increase in Wnt3a, β-catenin, Cyclin D1 and Wnt5a gene expressions, as well as, their protein levels. HP significantly prevented TAA-activated Wnt3a/β-catenin and Wnt5a pathways. Moreover, HP exerted hepatoprotective effect by significantly improving the oxidative imbalance, inflammation and liver function parameters, serum ALT, AST activities, and albumin level., Significance: Our study is the first to report the possible role of Wnt3a/β-catenin and Wnt5a pathways in TAA-induced early HCC model in rats. HP has a prophylactic effect against hepatocarcinogenesis via preventing the induction of both canonical and non-canonical Wnt pathways., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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