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Novel mTOR inhibitory activity of ciclopirox enhances parthenolide antileukemia activity

Siddhartha Sen1, Duane C Hassane, Cheryl Corbett

  • 1Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.

Experimental Hematology
|May 11, 2013
PubMed

Insights

Ciclopirox, an antifungal, shows new antitumor effects by inhibiting mTOR. This enhances parthenolide

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Ciclopirox, an antifungal, exhibits antitumor properties.
  • Its mechanism involves iron chelation and eIF5A inhibition.
  • The precise mechanism underlying its antitumor activity remains under investigation.

Purpose of the Study:

  • To identify a novel function of ciclopirox.
  • To investigate ciclopirox's effect on mTOR signaling.
  • To evaluate the combination of ciclopirox and parthenolide for acute myeloid leukemia treatment.

Main Methods:

  • Investigated ciclopirox's effect on mTOR activity.
  • Assessed the synergistic toxicity of ciclopirox and parthenolide against acute myeloid leukemia cells.
  • Differentiated ciclopirox's mTOR inhibition from iron chelation and eIF5A inhibition.

Main Results:

  • Ciclopirox was found to inhibit mTOR, a novel function.
  • The combination of ciclopirox and parthenolide showed enhanced toxicity against acute myeloid leukemia.
  • mTOR inhibition by ciclopirox is specific and not related to iron chelation or eIF5A inhibition.

Conclusions:

  • Ciclopirox possesses a novel mTOR-inhibiting function.
  • This mTOR inhibition may contribute to ciclopirox's antileukemic activity.
  • The combination therapy of ciclopirox and parthenolide shows promise for acute myeloid leukemia treatment.

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