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SHR Neuro Krebs Kardio Lipid

Hrzenjak, A; Reicher, H; Wintersperger, A; Steinecker-Frohnwieser, B; Sedlmayr, P; Schmidt, H; Nakamura, T; Malle, E; Sattler, W.
Inhibition of lung carcinoma cell growth by high density lipoprotein-associated alpha-tocopheryl-succinate.
CELL MOL LIFE SCI. 2004; 61(12): 1520-1531.
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Autor/innen der Med Uni Graz:
Hrzenjak Andelko
Malle Ernst
Reicher Helga
Sattler Wolfgang
Schmidt Helena
Sedlmayr Peter
Steinecker-Frohnwieser Bibiane
Wintersperger Andrea
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Abstract:
Alpha-tocopheryl-succinate (alphaTS) is a synthetic, anti-neoplastic derivative of alpha-tocopherol. Here we studied the effects of free and high-density lipoprotein subclass 3 (HDL3)-associated alphaTS on the growth of human (A549) and mouse Lewis (LL2) lung carcinoma cells. Both free and HDL3-associated alphaTS inhibited A549 growth in a time- and concentration-dependent manner. Treatment of A549 cells with alphaTS-enriched HDL3 led to DNA fragmentation and a time-dependent decrease in immunoreactivity of poly(ADP-ribose)polymerase. Uptake experiments revealed a high capacity for selective alphaTS uptake in excess of holoparticle endocytosis. Overexpression of scavenger receptor class B, type I (SR-BI), the prime receptor mediating selective lipid uptake, in A549 cells resulted in significantly increased selective alphaTS uptake, a finding associated with complete cellular growth arrest. The present in vitro findings were verified in an in vivo model: tumor inoculation in C57BL6 was performed with either wild-type, beta-galactosidase- or SR-BI-overexpressing LL2 cells. After tumor inoculation, the animals received six consecutive intravenous injections of alphaTS. This experimental setup resulted in significantly reduced tumor burden in animals that were inoculated with SR-BI-overexpressing LL2 cells but not in animals inoculated with wild-type or beta-galactocidase-transfected cells. Based on our in vitro and in vivo findings, we propose that SR-BI could provide a novel route for HDL3-mediated drug delivery of anti-neoplastic drugs.
Find related publications in this database (using NLM MeSH Indexing)
Adenoviridae - genetics
Animals - genetics
Antigens, CD36 - genetics
Carcinoma - drug therapy
Cell Division - drug therapy
Cell Line, Tumor - drug therapy
Centrifugation, Density Gradient - drug therapy
DNA Fragmentation - drug therapy
Dose-Response Relationship, Drug - drug therapy
Endocytosis - drug therapy
Humans - drug therapy
Hydrolysis - drug therapy
Immunohistochemistry - drug therapy
Lipoproteins, HDL - pharmacology
Lung Neoplasms - drug therapy
Mice - drug therapy
Mice, Inbred C57BL - drug therapy
Nucleosomes - metabolism
Poly(ADP-ribose) Polymerases - metabolism
Receptors, Immunologic - metabolism
Receptors, Scavenger - metabolism
Scavenger Receptors, Class B - metabolism
Time Factors - metabolism
Transfection - metabolism
Vitamin E - analogs and derivatives
beta-Galactosidase - metabolism

Find related publications in this database (Keywords)
HDL3
vitamin E-succinate
A549 cells
LL2 cells
SR-BI
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