Aspirin and indomethacin exhibit antiproliferative effects and induce apoptosis in T98G human glioblastoma cells

被引:28
作者
Amin, R
Kamitani, H
Sultana, H
Taniura, S
Islam, A
Sho, A
Ishibashi, M
Eling, TE
Watanabe, T
机构
[1] Tottori Univ, Sch Med, Dept Neurosurg, Inst Neurol Sci,Fac Med, Tottori 6838504, Japan
[2] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA
关键词
NSAIDs; T98G; COX; apoptosis; chemoprevention;
D O I
10.1179/016164103101201706
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The in vitro antiproliferative and apoptosis inducing properties of the nonsteroidal anti-inflammatory drugs (NSAIDs) like acetyl salicylic acid (aspirin) and indomethacin were investigated in T98G human glioblastoma cells to explore their potential role in the chemoprevention of human glioma. The biological effects induced by aspirin and indomethacin on T98G cells, in which the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were confirmed by RT-PCR and immunostaining, were investigated by studying cell proliferation and apoptosis assays. The antiproliferative effects occurred in a dose- and time-dependent manner on T98G cells by the treatment with 0.1 -2 mM aspirin and 25-100 muM indomethacin. Moreover, aspirin displayed the greatest growth inhibition within 24 h. Approximately 90% growth inhibition occurred following treatment either with 2 mM aspirin or 100 muM indomethacin by 72 h and induction of apoptosis was confirmed by DNA laddering and TUNEL assay. Our in vitro findings indicate that aspirin and indomethacin have an antiproliferative effect on T98G human glioblastoma cells at toxic concentrations.
引用
收藏
页码:370 / 376
页数:7
相关论文
共 33 条
[21]   EXPRESSION OF MESSENGER-RNA FOR CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 IN HUMAN TISSUES [J].
ONEILL, GP ;
FORDHUTCHINSON, AW .
FEBS LETTERS, 1993, 330 (02) :156-160
[22]   Selective potentiation of drug cytotoxicity by NSAID in human glioma cells:: The role of COX-1 and MRP [J].
Roller, A ;
Bähr, OR ;
Streffer, J ;
Winter, S ;
Heneka, M ;
Deininger, M ;
Meyermann, R ;
Naumann, U ;
Gulbins, E ;
Weller, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 259 (03) :600-605
[23]   Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection [J].
Rüschoff, J ;
Wallinger, S ;
Dietmaier, W ;
Bocker, T ;
Brockhoff, G ;
Hofstädter, F ;
Fishel, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) :11301-11306
[24]   SULINDAC SULFIDE, AN ASPIRIN-LIKE COMPOUND, INHIBITS PROLIFERATION, CAUSES CELL-CYCLE QUIESCENCE, AND INDUCES APOPTOSIS IN HT-29 COLON ADENOCARCINOMA CELLS [J].
SHIFF, SJ ;
QIAO, L ;
TSAI, LL ;
RIGAS, B .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) :491-503
[25]  
Shono T, 2001, CANCER RES, V61, P4375
[26]   The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action [J].
Smith, ML ;
Hawcroft, G ;
Hull, MA .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (05) :664-674
[27]   Preliminary individual adjuvant therapy for gliomas based on the results of molecular biological analyses for drug-resistance genes [J].
Tanaka, S ;
Kamitani, H ;
Amin, R ;
Watanabe, T ;
Oka, H ;
Fujii, K ;
Nagashima, T ;
Hori, T .
JOURNAL OF NEURO-ONCOLOGY, 2000, 46 (02) :157-171
[28]  
VEGA F, 1992, J NEURO-ONCOL, V13, P131
[29]   RANDOMIZED COMPARISONS OF RADIOTHERAPY AND NITROSOUREAS FOR THE TREATMENT OF MALIGNANT GLIOMA AFTER SURGERY [J].
WALKER, MD ;
GREEN, SB ;
BYAR, DP ;
ALEXANDER, E ;
BATZDORF, U ;
BROOKS, WH ;
HUNT, WE ;
MACCARTY, CS ;
MAHALEY, MS ;
MEALEY, J ;
OWENS, G ;
RANSOHOFF, J ;
ROBERTSON, JT ;
SHAPIRO, WR ;
SMITH, KR ;
WILSON, CB ;
STRIKE, TA .
NEW ENGLAND JOURNAL OF MEDICINE, 1980, 303 (23) :1323-1329
[30]  
Watson AJM, 1998, HISTOL HISTOPATHOL, V13, P591, DOI 10.14670/HH-13.591