Novel mTOR inhibitory activity of ciclopirox enhances parthenolide antileukemia activity Academic Article uri icon

Overview

MeSH Major

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antifungal Agents
  • Leukemia, Myeloid, Acute
  • Pyridones
  • Sesquiterpenes
  • TOR Serine-Threonine Kinases

abstract

  • Ciclopirox, an antifungal agent commonly used for the dermatologic treatment of mycoses, has been shown recently to have antitumor properties. Although the exact mechanism of ciclopirox is unclear, its antitumor activity has been attributed to iron chelation and inhibition of the translation initiation factor eIF5A. In this study, we identify a novel function of ciclopirox in the inhibition of mTOR. As with other mTOR inhibitors, we show that ciclopirox significantly enhances the ability of the established preclinical antileukemia compound, parthenolide, to target acute myeloid leukemia. The combination of parthenolide and ciclopirox demonstrates greater toxicity against acute myeloid leukemia than treatment with either compound alone. We also demonstrate that the ability of ciclopirox to inhibit mTOR is specific to ciclopirox because neither iron chelators nor other eIF5A inhibitors affect mTOR activity, even at high doses. We have thus identified a novel function of ciclopirox that might be important for its antileukemic activity.

publication date

  • September 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3809917

Digital Object Identifier (DOI)

  • 10.1016/j.exphem.2013.04.012

PubMed ID

  • 23660068

Additional Document Info

start page

  • 799

end page

  • 807.e4

volume

  • 41

number

  • 9