SP600125 inhibits Kv channels through a JNK-independent pathway in cancer cells.
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.
Martial
Sonia
S
Université de Nice Sophia Antipolis, Faculté des Sciences, Laboratoire de Biologie et de Physiopathologie des Systèmes Intégrés, CNRS FRE3094, UNSA, 28, Av Valrose, 06108, Nice, France.
Giorgelli
Jean-Luc
JL
Renaudo
Adrien
A
Derijard
Benoît
B
Soriani
Olivier
O
D000873:Anthracenes / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019169:Jurkat Cells; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000873:Anthracenes; D002934:Cinnamates; D003521:Cyclopropanes; D024642:Potassium Channels, Voltage-Gated; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C065310:igmesine