New insights on the use of desipramine as an inhibitor for acid ceramidase
Open Access
- 4 August 2006
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (19), 4751-4756
- https://doi.org/10.1016/j.febslet.2006.07.071
Abstract
Treatment of different cancer cell lines with desipramine induced a time‐ and dose‐dependent downregulation of acid ceramidase. Desipramine's effect on acid ceramidase appeared specific for amphiphilic agents (desipramine, chlorpromazine, and chloroquine) but not other lysomotropic agents such as ammonium chloride and bafilomycin A1, and was not transcriptionally regulated. The cathepsin B/L inhibitor, CA074ME, but not the cathepsin D inhibitor, pepstatin A, blocked desipramine's effect on acid ceramidase. Desipramine led to a more pronounced downregulation of sphingosine compared to ceramide suggesting acid ceramidase inhibition is important to desipramine's mechanism of action. This study reveals a new mechanism of action for desipramine.Keywords
This publication has 20 references indexed in Scilit:
- Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cellsBioorganic & Medicinal Chemistry, 2006
- Biologically active sphingolipids in cancer pathogenesis and treatmentNature Reviews Cancer, 2004
- Quantitative measurement of different ceramide species from crude cellular extracts by normal-phase high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometryRapid Communications in Mass Spectrometry, 2004
- Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramineFEBS Letters, 2004
- The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and inhibits tumor growth in prostate cancer xenograftsThe Prostate, 2003
- Oxidized Low Density Lipoprotein Inhibits Macrophage Apoptosis by Blocking Ceramide Generation, Thereby Maintaining Protein Kinase B Activation and Bcl-XL LevelsJournal of Biological Chemistry, 2003
- Ceramide Signaling in Fenretinide-induced Endothelial Cell ApoptosisPublished by Elsevier BV ,2002
- Overexpression of Acid Ceramidase Protects from Tumor Necrosis Factor–Induced Cell DeathThe Journal of Experimental Medicine, 2000
- Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistanceBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1995
- The Tricyclic Antidepressant Desipramine Causes Proteolytic Degradation of Lysosomal Sphingomyelinase in Human FibroblastsBiological Chemistry Hoppe-Seyler, 1994