High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells

Highlights • Drug efflux via membrane pumps is a resistant mechanism behind AML treatment failure. • Molecules with high affinity or covalent binding overcome pump efflux. • CTX-40 and zampanolide induce cell death in pump-overexpressing AML lines. • Both molecules synergize with daunorubicin withou...

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Bibliographic Details
Published in:Cancer letters 2015-11, Vol.368 (1), p.97-104
Main Authors: Pera, Benet, Calvo-Vidal, M. Nieves, Ambati, Srikanth, Jordi, Michel, Kahn, Alissa, Díaz, J. Fernando, Fang, Weishuo, Altmann, Karl-Heinz, Cerchietti, Leandro, Moore, Malcolm A.S
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Acute myeloid leukemia (AML)
Affinity
Animals
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - toxicity
Apoptosis - drug effects
Bone marrow
Cancer therapies
Cell Cycle Checkpoints - drug effects
Cell Proliferation - drug effects
Chemotherapy
Clinical trials
Covalence
Daunorubicin
Daunorubicin - pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm - drug effects
Drug Synergism
Hematology, Oncology and Palliative Medicine
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - pathology
Hemopoiesis
HL-60 Cells
Humans
Leukemia
Leukemia, Myeloid, Acute - metabolism
Leukemia, Myeloid, Acute - pathology
Ligands
Macrolides - pharmacology
Macrolides - toxicity
Mice
Microtubules
Microtubules - drug effects
Microtubules - metabolism
Microtubules - pathology
Myeloid leukemia
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
P-Glycoprotein
Paclitaxel
Paclitaxel - analogs & derivatives
Paclitaxel - pharmacology
Paclitaxel - toxicity
Proteins
Resistance
Time Factors
Toxicity
Tubulin Modulators - pharmacology
Tubulin Modulators - toxicity
Values
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Summary:Highlights • Drug efflux via membrane pumps is a resistant mechanism behind AML treatment failure. • Molecules with high affinity or covalent binding overcome pump efflux. • CTX-40 and zampanolide induce cell death in pump-overexpressing AML lines. • Both molecules synergize with daunorubicin without increasing hematopoietic toxicity. • CTX-40 and zampanolide keep their antileukemic activity in a primary sample.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2015.07.038