| Literature DB >> 16901483 |
Saeed Elojeimy1, David H Holman, Xiang Liu, Ahmed El-Zawahry, Maristella Villani, Joseph C Cheng, Ayman Mahdy, Youssef Zeidan, Alicja Bielwaska, Yusuf A Hannun, James S Norris.
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.Entities:
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Year: 2006 PMID： 16901483 DOI： 10.1016/j.febslet.2006.07.071
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124