New insights on the use of desipramine as an inhibitor for acid ceramidase

Saeed Elojeimy; 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

doi:10.1016/j.febslet.2006.07.071

New insights on the use of desipramine as an inhibitor for acid ceramidase

Saeed Elojeimy
, 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

Cancer Center

Medical University of South Carolina

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

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.

Original language	English
Pages (from-to)	4751-4756
Number of pages	6
Journal	FEBS Letters
Volume	580
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2006.07.071
State	Published - Aug 21 2006

Keywords

Acid ceramidase
Acid sphingomyelinase
Cationic amphiphilic drugs
Ceramide
Desipramine
Sphingomyelin

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10.1016/j.febslet.2006.07.071

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title = "New insights on the use of desipramine as an inhibitor for acid ceramidase",

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 = "Acid ceramidase, Acid sphingomyelinase, Cationic amphiphilic drugs, Ceramide, Desipramine, Sphingomyelin",

author = "Saeed Elojeimy and Holman, \{David H.\} and Xiang Liu and Ahmed El-Zawahry and Maristella Villani and Cheng, \{Joseph C.\} and Ayman Mahdy and Youssef Zeidan and Alicja Bielwaska and Hannun, \{Yusuf A.\} and Norris, \{James S.\}",

year = "2006",

month = aug,

day = "21",

doi = "10.1016/j.febslet.2006.07.071",

language = "English",

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pages = "4751--4756",

journal = "FEBS Letters",

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T1 - New insights on the use of desipramine as an inhibitor for acid ceramidase

AU - Elojeimy, Saeed

AU - Holman, David H.

AU - Liu, Xiang

AU - El-Zawahry, Ahmed

AU - Villani, Maristella

AU - Cheng, Joseph C.

AU - Mahdy, Ayman

AU - Zeidan, Youssef

AU - Bielwaska, Alicja

AU - Hannun, Yusuf A.

AU - Norris, James S.

PY - 2006/8/21

Y1 - 2006/8/21

N2 - 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.

AB - 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.

KW - Acid ceramidase

KW - Acid sphingomyelinase

KW - Cationic amphiphilic drugs

KW - Ceramide

KW - Desipramine

KW - Sphingomyelin

UR - https://www.scopus.com/pages/publications/33746897026

U2 - 10.1016/j.febslet.2006.07.071

DO - 10.1016/j.febslet.2006.07.071

M3 - Article

C2 - 16901483

AN - SCOPUS:33746897026

SN - 0014-5793

VL - 580

SP - 4751

EP - 4756

JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -

New insights on the use of desipramine as an inhibitor for acid ceramidase

Abstract

Keywords

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