Anticancer mechanism of troxerutin via targeting Nrf2 and NF-kappa B signalling pathways in hepatocarcinoma cell line

Thomas, Nisha Susan and George, Kiran and Selvam, Athavan Alias Anand (2019) Anticancer mechanism of troxerutin via targeting Nrf2 and NF-kappa B signalling pathways in hepatocarcinoma cell line. In: TOXICOLOGY IN VITRO, 54 . pp. 317-329.

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Abstract

Troxerutin (TX), a bioflavonoid widely present in various fruits and vegetables, has shown to exhibit numerous pharmacological properties including anti-neoplastic and anti-cancer activities. Nrf2 and NF-kappa B are the key transcription factors that regulate oxidative stress and inflammation, therefore we assessed whether TX modulate these pathways and its downstream proteins in HuH-7 hepatocarcinoma cells. TX induced apoptotic cellular and nuclear changes were examined by fluorescence staining techniques, agarose gel electrophoresis and flow cytometry. Oxidative stress was determined through biochemical analysis of antioxidant enzymes and lipid peroxidation profile. The protein expressions of NF-kappa B and Nrf2 pathway regulators, cell proliferation markers and apoptotic pathway mediators were evaluated by performing immunoblotting, immunocytochemistry and molecular docking. Our results revealed that TX inhibits the growth of HuH-7 cells in a concentration and time dependent manner. TX treated HuH-7 cells exhibited increased heme oxygenase (HO)-1 protein expression, augmented nuclear translocation of Nrf2, and reduced oxidative stress. Furthermore, TX suppressed the expression of IKK beta which subsequently inhibited the nuclear translocation of NF-kappa B (p65 subunit), and thus downregulated NF-kappa B mediated inflammatory responses, proliferation and cell survival. Collectively, our results indicate that TX exerts anti-cancer effect in HuH-7 hepatocarcinoma cells possibly through simultaneous regulation of the molecular signalling pathways, Nrf2 and NF-kappa B.

Item Type:	Journal Article
Publication:	TOXICOLOGY IN VITRO
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Additional Information:	Copyright of this article belongs to PERGAMON-ELSEVIER SCIENCE LTD
Keywords:	Troxerutin; Hepatocellular carcinoma; NF-kappa B; Nrf2; Apoptosis
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	28 Jan 2019 08:54
Last Modified:	28 Jan 2019 08:54
URI:	http://eprints.iisc.ac.in/id/eprint/61472

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