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Troxerutin subdues hepatic tumorigenesis via disrupting the MDM2-p53 interaction

Thomas, Nisha Susan and George, Kiran and Selvam, Athavan Alias Anand (2018) Troxerutin subdues hepatic tumorigenesis via disrupting the MDM2-p53 interaction. In: FOOD & FUNCTION, 9 (10). pp. 5336-5349.

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Official URL: http://dx.doi.org/10.1039/c8fo01111g

Abstract

Hepatocellular carcinoma (HCC) is the leading cause of cancer death worldwide that lacks proper medical prognosis and treatment. In the present study, the anti-tumoral potential of troxerutin (TX), an ethnomedicine, was examined in relation to its effects on the promoter 2-acetylaminofluorene (2-AAF) in N-nitrosodiethylamine (NDEA) initiated HCC, as compared to its effects on HCC induced by NDEA alone. Liver samples from each experimental group were collected and evaluated for histological, biochemical and cellular characterization. The protein expressions of apoptotic and cell proliferation markers were determined via immunohistochemistry and western blotting. Molecular docking was also performed to delineate the inhibitory mechanism of TX on HCC. The results show that only higher doses of TX showed a significant reduction in the incidence of hepatic nodule formation, and they also counteracted NDEA plus 2-AAF induced alterations in the enzymic status. The frequencies of glutathione-S-transferase and proliferating cell nuclear antigen, markers of S phase progression, were markedly reduced during TX treatment. TX also modulated the imbalance in the MDM2-p53 interaction. The molecular docking results confirmed the interaction of TX with the upstream kinases that regulate apoptosis. This study provides evidence that a copious dose of TX is required to counteract the differential mitoinhibitory effect of 2-AAF in NDEA initiated hepatomas, and TX exhibits an anti-tumoral effect via suppressing oxidative stress, regulating liver function enzymes, inhibiting inflammatory responses and modulating MDM2-p53 interactions, thus inducing apoptosis, and thereby suggesting that TX may provide promising therapeutic effects for the chemoprevention of HCC.

Item Type: Journal Article
Additional Information: Copy right for this article belong to ROYAL SOC CHEMISTR
Department/Centre: Division of Chemical Sciences > Organic Chemistry
Depositing User: Id for Latest eprints
Date Deposited: 14 Nov 2018 15:11
Last Modified: 14 Nov 2018 15:11
URI: http://eprints.iisc.ac.in/id/eprint/61061

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