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Cancer Res. 2004 Oct 1;64(19):6845-8.

Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts.

Author information

1
Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. melillog@ncifcrd.gov

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.

PMID:
15466170
DOI:
10.1158/0008-5472.CAN-04-2116
[Indexed for MEDLINE]
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