The Role of Sulforaphane in Microtubule Dynamics and Organisation in Health and Cancer

Mundy, Julia (2018) The Role of Sulforaphane in Microtubule Dynamics and Organisation in Health and Cancer. Masters thesis, University of East Anglia.

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The cellular cytoskeleton, composed of filamentous actin, intermediate filaments and microtubules, is integral in organisation of cell contents, connection of cells to the external environment and cell migration. Cytoskeletal changes and increased migration have been linked to the pathogenesis of multiple diseases, including cancer. The isothiocyanate sulforaphane has been shown in epidemiological studies to exhibit a range of chemopreventive and chemotherapeutic effects, and has attracted attention as a potential therapeutic agent. It has been previously demonstrated that sulforaphane exerts its chemotherapeutic effects via interaction with a number of cellular pathways and processes, including responses to oxidative stress, activation of apoptosis and chromatin remodelling, however, very little of this research focuses on potential effects on microtubules. Recently it has been proposed that sulforaphane is able to bind to, and potentially modify, tubulin leading to disrupted polymerisation of microtubules, which could result in aberrant division, transient cell cycle arrest, mitotic catastrophe and changes in cell migration. The proposed project aimed to investigate the effects of sulforaphane on cell migration and microtubules and upstream signalling proteins in both cancerous and non-cancerous epithelial cell lines. Significant reduction of scratch wound closure was observed at sulforaphane concentrations as low as 10µM, with reduction of both cell velocity and distance travelled. An upregulation of the GTPase activating protein Rap1GAP, a tumour suppressor gene, was observed at the mRNA and protein level following treatment of Panc-1 cells with sulforaphane, which could explain why migration is reduced in these cells, and could translate into an anti-metastatic mechanism in cancer therapies.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Jennifer Whitaker
Date Deposited: 10 Jun 2019 14:01
Last Modified: 27 Sep 2023 01:38

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