Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 591, Issue 1-3, Pages 102-105Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.06.062
Keywords
AML (Acute Myelocytic Leukaemia); PLK1 (Polo-Kinase 1); cell cycle; G2/M checkpoint
Categories
Funding
- Institut National du Cancer [PL103]
- C.N.R.S, I'Universite Paul Sabatier, la region Midi-Pyrenees
- Ligue Nationale Contre le Cancer
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Polo-Kinase 1 (PLK1) is a key cell cycle regulator that is necessary for checkpoint recovery after DNA damage-induced G2 arrest. We have examined the effects of PLK inhibition in Acute Myelocytic Leukaemia (AML) cells, whose resistance to genotoxic agents is thought to be associated with checkpoint reinforcement. We report that in U937 AML cells, PLK1 participates in checkpoint recovery, and that inhibition of PLK by the GW843682X compound results in mitotic accumulation and apoptosis. We also found that when challenged with VP-16, inhibition of PLK1 prevented U937 cells from checkpoint exit. Finally, we found that treatment with GW843682X slightly reduced genotoxic-induced inhibition of colony formation efficiency of primary leukaemia cells (CFU-L) from AML patients. (C) 2008 Elsevier B.V. All rights reserved.
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