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Anti-tumoural effects of PlgK1-5 are directly linked to reduced ICAM expression, resulting in hepatoma cell apoptosis.
- Source :
-
International Journal of Colorectal Disease . Aug2012, Vol. 27 Issue 8, p1029-1038. 10p. 1 Color Photograph, 7 Graphs. - Publication Year :
- 2012
-
Abstract
- Purpose: Angiostatin and angiostatin-like molecules are known as anti-angiogenic factors, which inhibit endothelial cell functions resulting in reduced tumour growth. Recent data indicate that these molecules, especially PlgK1-5, directly affect tumour cells, which could explain the strong anti-tumoural effects of PlgK1-5. Therefore, we have analysed whether PlgK1-5 alters tumour cell functions and expression levels of cell adhesion molecules in murine and human hepatoma cells in vitro and in vivo. Methods: First, effects on tumour growth, proliferation and apoptosis were investigated in vivo in a subcutaneous tumour model. In vitro, effects of PlgK1-5 on tumour cell apoptosis, clonal expansion, migration, corresponding ICAM expression and intracellular signal transduction in murine Hepa129 and human HuH7 hepatoma cells have been analysed. Results: In vivo, subcutaneous tumour growth was reduced by 75% in PlgK1-5-treated animals compared to the controls. This was accompanied by increased tumour cell apoptosis (up to 33%) and decreased tumour cell proliferation (by up to 21%). In vitro, PlgK1-5 induced apoptosis in hepatoma cells, corresponding to increased caspase-8 cleavage and reduced AKT phosphorylation. Migration and clonal expansion was also diminished in PlgK1-5-treated Hepa129, corresponding to decreased ICAM expression levels. Conclusions: Here, we show that PlgK1-5 directly affects tumour cells by decreasing cell adhesion resulting-at least partly-in apoptosis. This is mediated by altered intracellular signal transduction and by activation of the caspase cascade. These findings further underscore the potential therapeutic role of PlgK1-5 in the treatment of HCC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01791958
- Volume :
- 27
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- International Journal of Colorectal Disease
- Publication Type :
- Academic Journal
- Accession number :
- 77959273
- Full Text :
- https://doi.org/10.1007/s00384-012-1418-6