SP600125 inhibits Kv channels through a JNK-independent pathway in cancer cells

Biochem Biophys Res Commun. 2008 Feb 22;366(4):944-50. doi: 10.1016/j.bbrc.2007.12.027. Epub 2007 Dec 17.

Abstract

Kv channels represent new important targets for the control of cancer growth and a better understanding of their regulating pathways in cancer cells is necessary to develop therapeutic strategies. In this study, we have addressed the putative modulation of Kv by MAP kinases through a pharmacological approach. We have found that the commonly used JNK inhibitor SP600125 strongly inhibits Kv channels through a JNK-independent pathway, likely interacting directly with the channels at the external side of the membrane. Our results indicate that the use of this compound may produce misleading conclusions for the role of JNK in cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology*
  • Cell Line, Tumor
  • Cinnamates / pharmacology
  • Cyclopropanes / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Ion Channel Gating / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Jurkat Cells
  • Neoplasms / enzymology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anthracenes
  • Cinnamates
  • Cyclopropanes
  • Potassium Channels, Voltage-Gated
  • pyrazolanthrone
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • igmesine