Schedule-dependent inhibition of hypoxia-inducible factor-1α protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma …
A Rapisarda, J Zalek, M Hollingshead, T Braunschweig… - Cancer research, 2004 - AACR
A Rapisarda, J Zalek, M Hollingshead, T Braunschweig, B Uranchimeg, CA Bonomi…
Cancer research, 2004•AACRWe have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-
inducible factor (HIF)-1α protein accumulation by a DNA damage-independent mechanism.
Here, we report that daily administration of topotecan inhibits HIF-1α protein expression in
U251-HRE glioblastoma xenografts. Concomitant with HIF-1α 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 …
inducible factor (HIF)-1α protein accumulation by a DNA damage-independent mechanism.
Here, we report that daily administration of topotecan inhibits HIF-1α protein expression in
U251-HRE glioblastoma xenografts. Concomitant with HIF-1α 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 …
Abstract
We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1α protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1α protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1α 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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