Mycophenolic Acid Overcomes Imatinib and Nilotinib Resistance of Chronic Myeloid Leukemia Cells by Apoptosis or a Senescent-Like Cell Cycle Arrest
Open Access
- 23 February 2012
- journal article
- research article
- Published by Hindawi Limited in Leukemia Research and Treatment
- Vol. 2012, 1-9
- https://doi.org/10.1155/2012/861301
Abstract
We used K562 cells sensitive or generated resistant to imatinib or nilotinib to investigate their response to mycophenolic acid (MPA). MPA induced DNA damage leading to cell death with a minor contribution of apoptosis, as revealed by annexin V labeling (up to 25%). In contrast, cell cycle arrest and positive staining for senescence-associated β-galactosidase activity were detected for a large cell population (80%). MPA-induced cell death was potentialized by the inhibition of autophagy and this is associated to the upregulation of apoptosis. In contrast, senescence was neither decreased nor abrogated in autophagy deficient K562 cells. Primary CD34 cells from CML patients sensitive or resistant to imatinib or nilotinib respond to MPA although apoptosis is mainly detected. These results show that MPA is an interesting tool to overcome resistance in vitro and in vivo mainly in the evolved phase of the disease.Keywords
This publication has 39 references indexed in Scilit:
- Resveratrol Promotes Autophagic Cell Death in Chronic Myelogenous Leukemia Cells via JNK-Mediated p62/SQSTM1 Expression and AMPK ActivationCancer Research, 2010
- Differential Dependence on Beclin 1 for the Regulation of Pro-Survival Autophagy by Bcl-2 and Bcl-xL in HCT116 Colorectal Cancer CellsPLOS ONE, 2010
- The Necrotic Signal Induced by Mycophenolic Acid Overcomes Apoptosis-Resistance in Tumor CellsPLOS ONE, 2009
- Targeting autophagy potentiates tyrosine kinase inhibitor–induced cell death in Philadelphia chromosome–positive cells, including primary CML stem cellsJCI Insight, 2009
- Autophagy mediates the mitotic senescence transitionGenes & Development, 2009
- Autophagy and autophagic cell death are next targets for elimination of the resistance to tyrosine kinase inhibitorsCancer Science, 2008
- BRAFE600-associated senescence-like cell cycle arrest of human naeviNature, 2005
- SRCircumventing imatinib resistanceCancer Cell, 2004
- Activation of Caspase-2 Mediates the Apoptosis Induced by GTP-Depletion in Insulin-Secreting (HIT-T15) CellsEndocrinology, 2002
- Roots of Clinical Resistance to STI-571 Cancer TherapyScience, 2001