Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1H NMR spectroscopy

被引:73
作者
Bezabeh, T
Mowat, MRA
Jarolim, L
Greenberg, AH
Smith, ICP
机构
[1] Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada
[2] Univ Manitoba, Manitoba Inst Cell Biol, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
nuclear magnetic resonance spectroscopy; apoptosis; necrosis; HeLa cells; human cervical carcinoma;
D O I
10.1038/sj.cdd.4400802
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
Apoptosis and necrosis need to be differentiated in order to distinguish drug-induced cell death from spontaneous cell death due to hypoxia. The ability to differentiate between these two modes of cell death, especially at an early stage in the process, could have a significant impact on accessing the outcome of anticancer drug therapy in the clinic, Nuclear magnetic resonance spectroscopy was used to distinguish apoptosis from necrosis in human cervical carcinoma (Hela) cells. Apoptosis was induced by treatment with the topoisomerase II inhibitor etoposide, whereas necrosis was induced by the use of ethacrynic acid or cytochalasin B, We found that the intensity of the methylene resonance increases significantly as early as 6 h after the onset of apoptosis, but that no such changes occur during necrosis. The spectral intensity ratio of the methylene to methyl resonances also shows a high correlation with the percentage of apoptotic cells in the sample (r(2)=0.965, P < 0.003).
引用
收藏
页码:219 / 224
页数:6
相关论文
共 32 条
[1]  
Blankenberg FG, 1996, BLOOD, V87, P1951
[2]   Quantitative analysis of apoptotic cell death using proton nuclear magnetic resonance spectroscopy [J].
Blankenberg, FG ;
Katsikis, PD ;
Storrs, RW ;
Beaulieu, C ;
Spielman, D ;
Chen, JY ;
Naumovski, L ;
Tait, JF .
BLOOD, 1997, 89 (10) :3778-3786
[3]  
BOGIN L, 1998, BIOCHIM BIOPHYS ACTA, V1329, P217
[4]  
Cory S, 1999, CANCER RES, V59, p1685S
[5]  
COTTER TG, 1992, CANCER RES, V52, P997
[6]  
Delikatny EJ, 1996, INT J CANCER, V65, P238
[7]   ANALYSIS AND DISCRIMINATION OF NECROSIS AND APOPTOSIS (PROGRAMMED CELL-DEATH) BY MULTIPARAMETER FLOW-CYTOMETRY [J].
DIVE, C ;
GREGORY, CD ;
PHIPPS, DJ ;
EVANS, DL ;
MILNER, AE ;
WYLLIE, AH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1133 (03) :275-285
[8]   Signal transduction pathways that regulate cell survival and cell death [J].
Dragovich, T ;
Rudin, CM ;
Thompson, CB .
ONCOGENE, 1998, 17 (25) :3207-3213
[9]   A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [J].
Enari, M ;
Sakahira, H ;
Yokoyama, H ;
Okawa, K ;
Iwamatsu, A ;
Nagata, S .
NATURE, 1998, 391 (6662) :43-50
[10]  
Engelmann J, 1996, ANTICANCER RES, V16, P1429