Xanthohumol inhibits inflammatory factor production and angiogenesis in breast cancer xenografts
| Autor: | Raquel Soares, Fátima Gärtner, Sandra Pinheiro-Silva, Rosário Monteiro, Susana G. Guerreiro, Conceição Calhau, Artur Oliveira e Silva, Isabel Azevedo |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Angiogenesis Cell Survival Cell Mice Nude Breast Neoplasms Biology Biochemistry chemistry.chemical_compound Mice Cell Line Tumor medicine Animals Humans Molecular Biology Cell Proliferation Flavonoids Inflammation Propiophenones Cell Death Neovascularization Pathologic Cell growth NF-kappa B Transcription Factor RelA Cell Biology Immunohistochemistry Xenograft Model Antitumor Assays Tumor Burden Endothelial stem cell medicine.anatomical_structure chemistry Apoptosis Immunology Xanthohumol Cancer research Trypan blue Female Immunostaining |
| Zdroj: | Journal of cellular biochemistry. 104(5) |
| ISSN: | 1097-4644 |
| Popis: | Xanthohumol, a natural polyphenol present in beer, is known to exert anti-cancer effects. However, its precise mechanisms are not yet clearly defined. The aim of this study was to investigate the effect of oral administration of xanthohumol (XN) in breast cancer xenografts in nude mice. Proliferation and apoptosis were first examined in MCF7 cell cultures after incubation with XN by trypan blue exclusion assay, ( 3 H)-thymidine incorporation, KI67 immunostaining and TUNEL. Morphological and histological characteristics of tumours from XN-treated or control (vehicle-treated) mice were compared. Immunohistochemistry for proliferative, inflammatory and endothelial cell markers was performed and activation of nuclear factor kappa B (NFkB) pathway was assessed by ELISA. In vitro MCF7 cell proliferation decreased in a dose-dependent manner. Oral administration of XN to nude mice inoculated with MCF7 cells resulted in central necrosis within tumours, reduced inflammatory cell number, focal proliferation areas, increased percentage of apoptotic cells and decreased microvessel density. Anti-angiogenic effects of XN were further confirmed by immunoblotting for factor VIII expression in XN-treated tumours as compared to controls. Decreased immunostaining for NFkB, phosphorylated- inhibitor of kappa B and interleukin-1b were also observed as well as a significant decrease in NFkB activity to 60% of control values. These novel findings indicate that XN is able to target both breast cancer and host cells, namely inflammatory and endothelial cells, suggesting its potential use as a double-edge anti-cancer agent. J. Cell. Biochem. |
| Databáze: | OpenAIRE |
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