Abstract Title:

Hepatoprotective effect of hesperidin in hepatocellular carcinoma: Involvement of Wnt signaling pathways.

Abstract Source:

Life Sci. 2017 Jul 25. Epub 2017 Jul 25. PMID: 28754618

Abstract Author(s):

Randa A Zaghloul, Nehal M Elsherbiny, Hany I Kenawy, Amr El-Karef, Laila A Eissa, Mamdouh M El-Shishtawy

Article Affiliation:

Randa A Zaghloul


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 recombinantWnt3a (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.

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