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

Eur J Pharmacol. 1999 Apr 9;370(2):195-9. doi: 10.1016/s0014-2999(99)00155-7.


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, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Cell Survival / drug effects
  • Cytoskeleton / drug effects*
  • Cytoskeleton / metabolism
  • Dose-Response Relationship, Drug
  • Fructosediphosphates / metabolism*
  • Glucose-6-Phosphate / analogs & derivatives*
  • Glucose-6-Phosphate / metabolism
  • Glycolysis / drug effects
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / metabolism*
  • Mice
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Phosphofructokinase-1 / metabolism*


  • Antineoplastic Agents, Phytogenic
  • Fructosediphosphates
  • Glucose-6-Phosphate
  • Adenosine Triphosphate
  • glucose-1,6-bisphosphate
  • Phosphofructokinase-1
  • fructose-1,6-diphosphate
  • Paclitaxel