Inhibition of PDE3, PDE4 and PDE7 potentiates glucocorticoid-induced apoptosis and overcomes glucocorticoid resistance in CEM T leukemic cells

• Published in: Biochemical pharmacology Vol. 79; no. 3; pp. 321 - 329
• Main Authors: Dong, Hongli, Zitt, Christof, Auriga, Cornelia, Hatzelmann, Armin, Epstein, Paul M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2010; Elsevier
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; cAMP; Cyclic Nucleotide Phosphodiesterases, Type 3 - physiology; Cyclic Nucleotide Phosphodiesterases, Type 4 - physiology; Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors; Cyclic Nucleotide Phosphodiesterases, Type 7 - physiology; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - physiology; Drug Synergism; Glucocorticoids; Glucocorticoids - pharmacology; Hematologic and hematopoietic diseases; Humans; Jurkat Cells; Leukemia; Leukemia, T-Cell - drug therapy; Leukemia, T-Cell - enzymology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Phosphodiesterase; Phosphodiesterase 3 Inhibitors; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors - pharmacology; Tumor Cells, Cultured; Glucocorticoids; cAMP; Leukemia; Phosphodiesterase; Cyclic AMP; Malignant hemopathy; Glucocorticoid; Resistance; Cell death; T-Lymphocyte; AMP-3',5'; Inhibitor; Cancer; Apoptosis

This paper concerns the targeting of cyclic nucleotide phosphodiesterases (PDEs) to induce apoptosis and overcome glucocorticoid resistance of leukemic cells. Stimulation of the cAMP signaling pathway has been shown to induce apoptosis and augment the effects of glucocorticoids in inducing apoptosis...