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  • Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

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    Author(s)
    Yan, Bing
    Stantic, Marina
    Zobalova, Renata
    Bezawork-Geleta, Ayenachew
    Stapelberg, Michael
    Stursa, Jan
    Prokopova, Katerina
    Dong, Lanfeng
    Neuzil, Jiri
    Griffith University Author(s)
    Neuzil, Jiri
    Stapelberg, Michael
    Zobalova, Renata
    Stantic, Marina
    Dong, Lan-feng
    Yan, Bing
    Bezawork-Geleta, Ayenachew
    Year published
    2015
    Metadata
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    Abstract
    Background: Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. Methods: The mammosphere model ...
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    Background: Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. Methods: The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Results: Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2high tumours derived from breast TICs by inducing apoptosis in tumour cells. Conclusions: These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells.
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    Journal Title
    BMC Cancer
    Volume
    15
    DOI
    https://doi.org/10.1186/s12885-015-1394-7
    Copyright Statement
    © Yan et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
    Subject
    Oncology and Carcinogenesis not elsewhere classified
    Oncology and Carcinogenesis
    Public Health and Health Services
    Publication URI
    http://hdl.handle.net/10072/100775
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    • Journal articles

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