[Effect of decreased GSH on sensitivity of breast cancer cells to ADM].
OBJECTIVE
Glutathione(GSH) maintains an optimum cellular redox potential. Elevated levels of GSH render some types of cancer cells resistant against anti-cancer drugs. The aim of this study was to determine the effect of a thiol-depleting agent, diethylmaleate (DEM), on the sensitivity of human breast cancer cells to ADM.


METHODS
The ADM-resistant human breast cancer MCF-7/ADM cell lines and ADM-sensitive MCF-7/S cell lines were treated by thiol-depleting agent DEM for 3 h respectively. The changes of sensitivity to ADM were then measured by MTT assay. The intracellular GSH contents were examined by fluorescent-spectrophotometry and the correlation between the changes of sensitivity to ADM and the intracellular GSH content was analyzed.


RESULTS
Treatment of MCF-7/ADM and MCF-7/S cells by 0.1 micromol/L DEM for 3 h decreased 37.4% and 29.7% of the intracellular GSH content respectively (P < 0.01). ADM also decreased intracellular GSH content in a ADM-concentration-dependent manner. The combined use of DEM and ADM depleted the intracellular GSH content in both cells significantly more than the sum of single use of ADM and DEM alone. The sensitivity of both cells to ADM increased with the decline of intracellular GSH content.


CONCLUSIONS
The depletion effect of DEM on the intracellular GSH could be enhanced by ADM and such depletion may be involved in the changes of the sensitivity of MCF/7 cells to ADM.
Han
Xiao-qun
XQ
West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Li
Zhu-hua
ZH
Zhang
Jing-ge
JG
Jiang
Yi-deng
YD
Peng
Ke-jun
KJ
Wang
Li-zhen
LZ
Wang
Shu-ren
SR
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008298:Maleates / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D008298:Maleates; D004317:Doxorubicin; C014476:diethyl maleate; D005978:Glutathione