A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts
| العنوان: | A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts |
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| المؤلفون: | Hiroshi Sonoo, Shiro Akinaga, Shiro Soga, Masafumi Kurosumi, Junichi Kurebayashi, Takemi Otsuki |
| المصدر: | Japanese Journal of Cancer Research : Gann |
| بيانات النشر: | Blackwell Publishing Ltd, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Cancer Research, Time Factors, Angiogenesis, medicine.medical_treatment, Apoptosis, Endothelial Growth Factors, chemistry.chemical_compound, Lactones, Mice, Breast cancer, Tumor Cells, Cultured, Hypoxia, Lymphokines, Neovascularization, Pathologic, Vascular Endothelial Growth Factors, Nuclear Proteins, Radicicol, Vascular endothelial growth factor, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Vascular endothelial growth factor A, Oncology, Hypoxia-inducible factors, Female, Hypoxia-Inducible Factor 1, Macrolides, Growth inhibition, Cell Division, medicine.medical_specialty, Blotting, Western, Transplantation, Heterologous, Mice, Nude, Breast Neoplasms, Biology, Article, Internal medicine, medicine, Animals, Humans, RNA, Messenger, Dose-Response Relationship, Drug, Growth factor, Radicicol Derivative KF58333, Hypoxia-Inducible Factor 1, alpha Subunit, Endocrinology, Ki-67 Antigen, chemistry, Hypoxia‐inducible factor‐1, Cancer research, Neoplasm Transplantation, Transcription Factors |
| الوصف: | A novel oxime derivative of radicicol, KF58333, binds to the heat shock protein 90 (Hsp90) and destabilizes its associated signaling molecules. These effects play a critical role in the growth inhibition of tumor cells. To further investigate the effects of this agent, it was administered to two human breast cancer cell lines, KPL-1 and KPL-4, both in vitro and in vivo. KF58333 dose-dependently inhibited the growth and vascular endothelial growth factor (VEGF) secretion, concomitantly with a decrease in VEGF mRNA expression, in each cell line. This agent also suppressed the increase of VEGF secretion and expression induced by hypoxia (1% O(2)). Intravenous injections of this agent into nude mice bearing either KPL-1 or KPL-4 xenografts significantly inhibited the tumor growth associated with a decrease in the Ki67 labeling index and microvascular area and an increase in apoptosis and the necrotic area. These findings indicate that the antitumor activity of this radicicol derivative may be partly mediated by decreasing VEGF secretion from tumor cells and inhibiting tumor angiogenesis. To explore the action mechanisms of the anti-angiogenic effect, the expression level of hypoxia-inducible factor (HIF)-1alpha was investigated. KF58333 provided a significant decrease in the HIF-1alpha protein expression under both normoxic and hypoxic conditions. In contrast, the mRNA expression of HIF-1alpha was not decreased by this agent. It is suggested that the post-transcriptional down-regulation of HIF-1alpha expression by this agent may result in a decrease of VEGF expression and tumor angiogenesis. |
| اللغة: | English |
| تدمد: | 1876-4673 0910-5050 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f269ab065e4afaeb4e7403630af32da6 http://europepmc.org/articles/PMC5926684 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f269ab065e4afaeb4e7403630af32da6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18764673 09105050 |
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