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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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SYSNO ASEP 0446714 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner Author(s) Yan, B. (AU)
Stantic, M. (AU)
Zobalová, Renata (BTO-N) RID
Bezawork-Geleta, A. (AU)
Stapelberg, M. (AU)
Stursa, J. (CZ)
Prokopová, Kateřina (BTO-N) ORCID
Dong, L. (AU)
Neužil, Jiří (BTO-N) RIDSource Title Bmc Cancer. - : BioMed Central
Roč. 15, č. 401 (2015)Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords Tumour-initiating cells ; Mitochondrially targeted vitamin E succinate ; Complex II Subject RIV FD - Oncology ; Hematology R&D Projects NT14078 GA MZd - Ministry of Health (MZ) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 UT WOS 000354932800001 DOI 10.1186/s12885-015-1394-7 Annotation 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 HER2(high) 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2016
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