Gemcitabine-mediated apoptosis is associated with increased CD95 surface expression but is not inhibited by DN-FADD in Colo357 pancreatic cancer cells

被引：20

作者：

Christgen, M ^{[1
]}

Schniewind, B ^{[1
]}

Jueschke, A ^{[1
]}

Ungefroren, H ^{[1
]}

Kalthoff, H ^{[1
]}

机构：

[1] Univ Kiel, Mol Oncol Res Grp, Clin Gen & Thorac Surg, D-24105 Kiel, Germany

来源：

CANCER LETTERS | 2005年 / 227卷 / 02期

关键词：

gemcitabine; pancreatic cancer; CD95/FAS/Apo-1; caspase-8; FADD;

D O I：

10.1016/j.canlet.2005.01.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study investigates the role of caspase-8 and DN-FADD, an inhibitor of CD95-dependent caspase-8 activation, in gemcitabine-induced apoptosis of Colo357 pancreatic cancer cells. Gemcitabine-mediated apoptosis was monitored by the kinetics of caspase-8 activation and cytochrome c release. Gemcitabine treatment of Colo357 cells increased CD95 surface expression, raising the possibility of the involvement of CD95 in gemcitabine-mediated caspase-8 activation. However, ectopic expression of DN-FADD and treatment of cells with the antagonistic anti-CD95 antibody Z134 both failed to suppress gemcitabine-induced apoptosis but substantially inhibited CD95-mediated apoptosis. DN-FADD, which surprisingly accumulated in nuclei of Colo357 cells, was unable to block caspase-8 activation mediated by either gemcitabine or CD95. These observations argue against a role of CD95 in gemcitabine-induced caspase-8 activation and reveal that the anti-apoptotic function of DN-FADD differs from caspase-8 inhibition in Colo357 cells. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：193 / 200

页数：8

共 21 条

[1] Inhibitor of apoptosis-1 (IAP-1) expression and apoptosis in non-small-cell lung cancer cells exposed to gemcitabine [J].

Bandala, E ;

Espinosa, M ;

Maldonado, V ;

Meléndez-Zajgla, J .

BIOCHEMICAL PHARMACOLOGY, 2001, 62 (01) :13-19

[2] The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation [J].

Belka, C ;

Marini, P ;

Lepple-Wienhues, A ;

Budach, W ;

Jekle, A ;

Los, M ;

Lang, F ;

Schulze-Osthoff, K ;

Gulbins, E ;

Bamberg, M .

ONCOGENE, 1999, 18 (35) :4983-4992

[3] Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death [J].

Boldin, MP ;

Goncharov, TM ;

Goltsev, YV ;

Wallach, D .

CELL, 1996, 85 (06) :803-815

[4] Phase II study of gemcitabine in patients with advanced pancreatic cancer [J].

Carmichael, J ;

Fink, U ;

Russell, RCG ;

Spittle, MF ;

Harris, AL ;

Spiessi, G ;

Blatter, J .

BRITISH JOURNAL OF CANCER, 1996, 73 (01) :101-105

[5] De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells -: Dependence on protein phosphatase-1 [J].

Chalfant, CE ;

Rathman, K ;

Pinkerman, RL ;

Wood, RE ;

Obeid, LM ;

Ogretmen, B ;

Hannun, YA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) :12587-12595

[6]

CHANG GC, 2004, EUR J PHARMACOL, P2183

[7]

Chinnaiyan AM, 1996, J BIOL CHEM, V271, P4961

[8]

Ferreira CG, 2000, CANCER RES, V60, P7133

[9]

Ferreira CG, 2000, CLIN CANCER RES, V6, P203

[10] Molecular evidence for the nuclear localization of FADD [J].

Gómez-Angelats, M ;

Cidlowski, JA .

CELL DEATH AND DIFFERENTIATION, 2003, 10 (07) :791-797

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