Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Liu, Peng, Wang, Wei, Zhou, Zhigang, Smith, Andrew, Bowater, Richard P, Wormstone, Ian Michael, Chen, Yuqiong and Bao, Yongping (2018) Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells. Nutrients, 10 (5). ISSN 2072-6643

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    Abstract

    Sulforaphane (SFN) exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs) and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H₂O₂ challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the induction of intracellular glutathione (GSH) played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

    Item Type: Article
    Uncontrolled Keywords: sulforaphane,chemoprevention,sulforaphane metabolites,nrf2 or nuclear factor erythroid 2 [nf-e2]-related factor 2,gsh
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Faculty of Science > School of Biological Sciences
    Depositing User: Pure Connector
    Date Deposited: 25 May 2018 15:30
    Last Modified: 09 Apr 2019 13:24
    URI: https://ueaeprints.uea.ac.uk/id/eprint/67188
    DOI: 10.3390/nu10050585

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