Abstract |
We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue. These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients.
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Authors | Annamaria Rapisarda, Jessica Zalek, Melinda Hollingshead, Till Braunschweig, Badarch Uranchimeg, Carrie A Bonomi, Suzanne D Borgel, John P Carter, Stephen M Hewitt, Robert H Shoemaker, Giovanni Melillo |
Journal | Cancer research
(Cancer Res)
Vol. 64
Issue 19
Pg. 6845-8
(Oct 01 2004)
ISSN: 0008-5472 [Print] United States |
PMID | 15466170
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Enzyme Inhibitors
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Topoisomerase I Inhibitors
- Transcription Factors
- Topotecan
- Luciferases
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage)
- Cell Division
(drug effects)
- Cell Line, Tumor
- Drug Administration Schedule
- Enzyme Inhibitors
(pharmacology)
- Female
- Glioblastoma
(blood supply, drug therapy, metabolism, pathology)
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
- Luciferases
(antagonists & inhibitors, biosynthesis, genetics)
- Mice
- Mice, Nude
- Neovascularization, Pathologic
(drug therapy, metabolism)
- Topoisomerase I Inhibitors
- Topotecan
(administration & dosage)
- Transcription Factors
(antagonists & inhibitors, biosynthesis, genetics)
- Xenograft Model Antitumor Assays
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