Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pussinen, PJ; Lindner, H; Glatter, O; Reicher, H; Kostner, GM; Wintersperger, A; Malle, E; Sattler, W.
Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells.
BBA-MOL CELL BIOL LIPIDS 2000 1485: 129-144.
Doi: 10.1016/S1388-1981(00)00035-4
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Sattler Wolfgang
- Co-Autor*innen der Med Uni Graz
- Hinteregger Helga
- Kostner Gerhard
- Malle Ernst
- Wintersperger Andrea
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis - drug effects
- Breast Neoplasms - drug effects
- Cell Division - drug effects
- Female - drug effects
- Humans - drug effects
- Hydrolysis - drug effects
- Lipoproteins, HDL - metabolism
- Lipoproteins, LDL - metabolism
- Lipoproteins, VLDL - metabolism
- Mice - metabolism
- Receptors, LDL - metabolism
- Tumor Cells, Cultured - metabolism
- Vitamin E - analogs and derivatives
- Find related publications in this database (Keywords)
- vitamin E-succinate
- lipoprotein
- apoptosis
- carcinoma cell