Involvement of sphingolipids in apoptin-induced cell killing

X Liu; Y H Zeidan; S Elojeimy; D H Holman; A M El-Zawahry; G W Guo; A Bielawska; J Bielawski; Z Szulc; S Rubinchik; J Y Dong; T E Keane; M Tavassoli; Y A Hannun; J S Norris

doi:10.1016/j.ymthe.2006.07.001

Involvement of sphingolipids in apoptin-induced cell killing

X Liu, Y H Zeidan, S Elojeimy, D H Holman, A M El-Zawahry, G W Guo, A Bielawska, J Bielawski, Z Szulc, S Rubinchik, J Y Dong, T E Keane, M Tavassoli, Y A Hannun, J S Norris

Centre for Host Microbiome Interactions

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

32 Citations (Scopus)

Abstract

The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 mu M) attenuated (30%; P

Original language	English
Pages (from-to)	627 - 636
Number of pages	10
Journal	Molecular Therapy
Volume	14
Issue number	5
DOIs	https://doi.org/10.1016/j.ymthe.2006.07.001
Publication status	Published - Nov 2006

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10.1016/j.ymthe.2006.07.001

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title = "Involvement of sphingolipids in apoptin-induced cell killing",

abstract = "The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 mu M) attenuated (30%; P",

author = "X Liu and Zeidan, {Y H} and S Elojeimy and Holman, {D H} and El-Zawahry, {A M} and Guo, {G W} and A Bielawska and J Bielawski and Z Szulc and S Rubinchik and Dong, {J Y} and Keane, {T E} and M Tavassoli and Hannun, {Y A} and Norris, {J S}",

year = "2006",

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doi = "10.1016/j.ymthe.2006.07.001",

language = "English",

volume = "14",

pages = "627 -- 636",

journal = "Molecular Therapy",

issn = "1525-0024",

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T1 - Involvement of sphingolipids in apoptin-induced cell killing

AU - Liu, X

AU - Zeidan, Y H

AU - Elojeimy, S

AU - Holman, D H

AU - El-Zawahry, A M

AU - Guo, G W

AU - Bielawska, A

AU - Bielawski, J

AU - Szulc, Z

AU - Rubinchik, S

AU - Dong, J Y

AU - Keane, T E

AU - Tavassoli, M

AU - Hannun, Y A

AU - Norris, J S

PY - 2006/11

Y1 - 2006/11

N2 - The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 mu M) attenuated (30%; P

AB - The potential anti-tumor agent Apoptin activates apoptosis in many human cancers and transformed cell lines, but is believed to be less potent in primary cells. Although caspase 3 is activated during apoptin-induced apoptosis, the mechanism of tumor cell killing remains elusive. We now show that apoptin-mediated cell death involves modulation of the sphingomyelin-ceramide pathway. Treating cells with Ad-GFPApoptin resulted in increased ceramide accumulation and enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin. Using confocal microscopy, ASMase, normally present in the endosomal/lysosomal compartment, was observed to translocate to the cell's periphery. Cotreatment of Ad-GFPApoptin-infected cells with the ASMase inhibitor desipramine (2.5 mu M) attenuated (30%; P

U2 - 10.1016/j.ymthe.2006.07.001

DO - 10.1016/j.ymthe.2006.07.001

M3 - Article

SN - 1525-0024

VL - 14

SP - 627

EP - 636

JO - Molecular Therapy

JF - Molecular Therapy

IS - 5

ER -

Involvement of sphingolipids in apoptin-induced cell killing

Abstract

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