Sensitization of mesothelioma to TRAIL apoptosis by inhibition of histone deacetylase:: role of Bcl-xL down-regulation

被引:79
作者
Neuzil, H [1 ]
Swettenham, E [1 ]
Gellert, N [1 ]
机构
[1] Griffith Univ, Sch Hlth Sci, Southport, Qld, Australia
关键词
TRAIL; apoptosis; sensitization; histone deacetylase inhibitor;
D O I
10.1016/j.bbrc.2003.12.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The TNF-related apoptosis-inducing ligand (TRAIL) is an immunological inducer of apoptosis selectively killing many, but not all, cancer cells. Malignant mesothelioma (MM) is fatal neoplasia with no current treatment, most likely due to high resistance of MM cells towards inducers of apoptosis, including TRAIL. We studied whether inhibition of historic deacetylase (HDAC), recently shown to sensitize malignant cells to a variety of apoptogenic substances, renders MM cells susceptible to TRAIL. Indeed, subapoptotic doses of the HDAC inhibitor suberohydroxamic acid (SBHA) sensitized MM cells to TRAIL apoptosis. Of the apoptotic mediators tested, the anti-apoptotic protein Bcl-X-L was strongly down-regulated by combined treatment of the cells with SBHA and TRAIL but not by the HDAC inhibitor alone, while little or no change in the expression of other Bcl-2 family members highly expressed in MM cells, including Mcl-1 and Bax, was observed. Our data suggest a cross-talk between HDAC inhibition and TRAIL that results in modulation of expression of specific apoptotic mediators, and point to the potential of their combinatorial use in treatment of TRAIL-resistant neoplastic disease. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:186 / 191
页数:6
相关论文
共 32 条
[1]   Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection [J].
Alleva, R ;
Tomasetti, M ;
Andera, L ;
Gellert, N ;
Borghi, B ;
Weber, C ;
Murphy, MP ;
Neuzil, J .
FEBS LETTERS, 2001, 503 (01) :46-50
[2]   Apoptosis control by death and decoy receptors [J].
Ashkenazi, A ;
Dixit, VM .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (02) :255-260
[3]   Predictive and prognostic factors in malignant pleural mesotheliorna [J].
Baas, P .
CURRENT OPINION IN ONCOLOGY, 2003, 15 (02) :127-130
[4]   Rel/NF-κB transcription factors protect against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by up-regulating the TRAIL decoy receptor DcR1 [J].
Bernard, D ;
Quatannens, B ;
Vandenbunder, B ;
Abbadie, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (29) :27322-27328
[5]  
Boersma AWM, 1996, CYTOMETRY, V24, P123, DOI 10.1002/(SICI)1097-0320(19960601)24:2<123::AID-CYTO4>3.0.CO
[6]  
2-K
[7]   Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma [J].
Cao, XBX ;
Mohuiddin, I ;
Ece, F ;
McConkey, DJ ;
Smythe, WR .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2001, 25 (05) :562-568
[8]  
CARBONE M, 1994, ONCOGENE, V9, P1781
[9]   Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma [J].
Gordon, GJ ;
Appasani, K ;
Parcells, JP ;
Mukhopadhyay, NK ;
Jaklitsch, MT ;
Richards, WG ;
Sugarbaker, DJ ;
Bueno, R .
CARCINOGENESIS, 2002, 23 (06) :1017-1024
[10]   Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl-2 and Bcl-xL antisense treatment [J].
Hopkins-Donaldson, S ;
Cathomas, R ;
Simoes-Wüst, AP ;
Kurtz, S ;
Belyanskya, L ;
Stahel, RA ;
Zangemeister-Wittke, U .
INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (02) :160-166