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Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells.

Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Research Abstract Details 

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  • Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Abstract Text:

    p j pussinenP J Pussinen,h lindnerH Lindner,o glatterO Glatter,h reicherH Reicher,g m kostnerG M Kostner,a winterspergerA Wintersperger,e malleE Malle,w sattlerW Sattler,

    alpha-Tocopheryl succinate (alpha-TS) is a potent inhibitor of tumor cell proliferation. The goal of the present study was to investigate whether and to what extent alpha-TS associates with plasma lipoproteins and if alpha-TS-enriched lipoproteins inhibit breast cancer cell growth in a manner comparable to the free drug. In vitro enrichment of human plasma revealed that alpha-TS readily associated with the main lipoprotein classes, findings confirmed in vivo in mice. At the highest alpha-TS concentrations, lipoproteins carrying 50000 (VLDL), 5000 (LDL) and 700 (HDL) alpha-TS molecules per lipoprotein particle were generated. alpha-TS enrichment generated lipoprotein particles with slightly decreased density and increased particle radius. To study whether the level of LDL-receptor (LDL-R) expression affects alpha-TS uptake from apoB/E containing lipoprotein particles human breast cancer cells with low (MCF-7) and normal (HBL-100) LDL-R expression were used. The uptake of free, VLDL- and (apoE-free) HDL(3)-associated alpha-TS was nearly identical for both cell lines. In contrast, uptake of LDL-associated alpha-TS by HBL-100 cells (normal LDL-R expression) was about twice as high as compared to MCF-7 cells (low LDL-R expression). VLDL and LDL-associated alpha-TS inhibited proliferation most effectively at the highest concentration of alpha-TS used (100% inhibition of MCF-7 growth with 20 microg/ml of lipoprotein-associated alpha-TS). However, also alpha-TS-free VLDL and LDL inhibited HBL-100 cell proliferation up to 55%. In both cell lines, alpha-TS-enriched HDL(3) inhibited cell growth by 40-60%. Incubation of both cell lines in the presence of free or lipoprotein-associated alpha-TS resulted in DNA fragmentation indicative of apoptosis. Collectively, the present findings demonstrate that: (1) alpha-TS readily associates with lipoproteins in vitro and in vivo; (2) the lipoprotein-enrichment efficacy was dependent on the particle size and/or the triglyceride content of the lipoprotein; (3) uptake of LDL-associated alpha-TS was apparently dependent on the level of LDL-R expression; and (4) lipoproteins were efficient alpha-TS carriers inducing reduced cell proliferation rates and apoptosis in human breast cancer cells as observed for the free drug.

    Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Publishing Authors By Initials

    pj pussinenPJ Pussinen,h lindnerH Lindner,o glatterO Glatter,h reicherH Reicher,gm kostnerGM Kostner,a winterspergerA Wintersperger,e malleE Malle,w sattlerW Sattler,

    For similar heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: vitamin e research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: vitamin e research

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    Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Biochimica et biophysica acta

    VOLUME: 1485

    Page Numbers: 129-44

    Journal Abbreviation: Biochim. Biophys. Acta

    ISSN: 0006-3002

    DAY: 31

    MONTH: May

    YEAR: 2000

    Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 217513

    Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Keywords Mesh Terms:

    KEYWORDS: Vitamin E

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Information

    Substance Name: tocopherol succinate

    Registry Number: 17407-37-3

    Grant and Affiliation Information for Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells.

    AFFILIATION: Institute of Medical Biochemistry, Graz, Austria.

    Country: NETHERLANDS

    NETHERLANDS Research PublicationNETHERLANDS Research Publication

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    MEDLINETA: Biochim Biophys Acta

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