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Antitumor activity of cationic liposome-mediated Bax gene transfer in osteosarcoma cells: induction of apoptosis and caspase-independent cell death.

Abstract
The purpose of this study was to evaluate the anti-tumor effects of osteosarcoma (HOSM-1) cells via transfer of the Bax gene using a cationic liposome. We evaluated the levels of Bax, Bcl-xL, Bcl-2 and cytochrome c expression by Western blot analysis, and caspase-9 and -3 activities were determined in a colorimetric assay. Apoptosis was detected using a TUNEL assay, and cell growth inhibition was determined in an MTT assay. Following Bax gene transfer, release of cytochrome c to the cytosol was detected, the activities of caspase-9 and -3 increased, and TUNEL-positive cells (37.5%) were detected. Cell survival rate was 50.8% under these conditions. Induction of apoptosis was inhibited by a caspase inhibitor (zVAD-fmk), but only a slight increase in cell survival rate occurred. Hence, since not only apoptosis but also caspase-independent cell death is induced in HOSM-1 cells, we anticipate that Bax gene therapy with cationic liposomes will be useful for osteosarcoma.
AuthorsKenya Okumura, Minoru Nakase, Shinnosuke Nakamura, Madoka Inui, Kenichi Hiramoto, Toshiro Tagawa
JournalInternational journal of oncology (Int J Oncol) Vol. 27 Issue 2 Pg. 433-8 (Aug 2005) ISSN: 1019-6439 [Print] Greece
PMID16010425 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cations
  • Liposomes
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases
Topics
  • Amino Acid Chloromethyl Ketones (pharmacology)
  • Apoptosis (drug effects, genetics)
  • Blotting, Western
  • Caspase 3
  • Caspase 9
  • Caspase Inhibitors
  • Caspases (metabolism)
  • Cations (chemistry)
  • Cell Line, Tumor
  • Cell Survival (drug effects, genetics)
  • Humans
  • In Situ Nick-End Labeling
  • Liposomes (chemistry)
  • Osteosarcoma (enzymology, genetics, pathology)
  • Transfection (methods)

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