| Taxol (paclitaxel) induces a detachment of phosphofructokinase from cytoskeleton of melanoma cells and decreases the levels of glucose 1,6-bisphosphate, fructose 1,6-bisphosphate and ATP. | |
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MedLine Citation:
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PMID: 10323269 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucose utilization through glycolysis, which is the primary energy source in cancer cells, is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. Here we report of a novel mechanism of action of taxol (paclitaxel; Baccatin III N-benzyl-beta-phenylisoserine ester), the anti-microtubule agent with remarkable anticancer activity. We show that taxol affects both levels of regulation of glycolysis in melanoma cells; it decreases the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two allosteric stimulatory signal molecules of glycolysis, and also causes a detachment of phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), the rate-limiting enzyme of glycolysis, from the cytoskeleton of B16 melanoma cells. These effects of taxol were dose-dependent, and preceded the decrease in ATP levels and cell viability. Thus, taxol not only inhibits the essential dynamic processes of microtubule network, but also reduces glycolysis, through the novel mechanisms described here. |
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Authors:
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L Glass-Marmor; R Beitner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 370 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-07-16 Completed Date: 1999-07-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 195-9 Citation Subset: IM |
Affiliation:
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Health Sciences Research Center, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Antineoplastic Agents, Phytogenic / pharmacology*, therapeutic use Cell Survival / drug effects Cytoskeleton / drug effects*, metabolism Dose-Response Relationship, Drug Fructosediphosphates / metabolism* Glucose-6-Phosphate / analogs & derivatives*, metabolism Glycolysis / drug effects Melanoma, Experimental / drug therapy, metabolism* Mice Paclitaxel / pharmacology*, therapeutic use Phosphofructokinase-1 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Fructosediphosphates; 0/glucose-1,6-bisphosphate; 33069-62-4/Paclitaxel; 488-69-7/fructose-1,6-diphosphate; 56-65-5/Adenosine Triphosphate; 56-73-5/Glucose-6-Phosphate; EC 2.7.1.11/Phosphofructokinase-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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