EFFECTS OF TAMOXIFEN ON GROWTH AND APOPTOSIS OF ESTROGEN-DEPENDENT AND ESTROGEN-INDEPENDENT HUMAN BREAST-CANCER CELLS

被引：150

作者：

PERRY, RR

KANG, Y

GREAVES, B

机构：

[1] Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, 23507-1912, VA

来源：

ANNALS OF SURGICAL ONCOLOGY | 1995年 / 2卷 / 03期

关键词：

APOPTOSIS; TAMOXIFEN; BREAST CANCER; MCF-7; CELLS; MDA-231;

D O I：

10.1007/BF02307030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Apoptosis (''programmed cell death'') is an active process characterized by prominent nuclear changes and DNA cleavage, which distinguishes it from cellular necrosis. In this study we investigated whether tamoxifen (TAM) treatment of estrogen receptor ER(+) MCF-7 and ER(-) MDA-231 human breast cancer cells resulted in cytotoxicity and cellular changes typical of apoptosis. Methods: Cytotoxicity was measured using a tetrazolium assay. Cellular morphologic changes were observed using transmission electron microscopy. DNA cleavage was assessed using 1.6% agarose gel electrophoresis and was also quantitated biochemically. Results: Exposure of cells to TAM for 24 h resulted in dose- dependent cytotoxicity, and MCF-7 cells were somewhat more sensitive to TAM. TAM induced chromatin condensation around the nuclear periphery in both cell lines, changes typical of apoptosis. TAM-induced cytotoxicity correlated with dose-dependent DNA cleavage, which showed the characteristic ''internucleosomal ladder.'' DNA. cleavage occurred at a slightly lower TAM dose and occurred somewhat sooner in MCF-7 cells. TAM-induced DNA cleavage in MCF-7 cells was inhibited by the protein synthesis inhibitor cycloheximide, the RNA synthesis inhibitor actinomycin D, and by 17 beta-estradiol. However, in MDA-231 cells, DNA cleavage was inhibited by cycloheximide, partially but not significantly inhibited by actinomycin D, and not inhibited by 17 beta-estradiol. Conclusions: TAM induces typical apoptosis in ER(+) or ER(-) human breast cancer cells. TAM induction of apoptosis in MCF-7 cells involves the estrogen receptor, and requires the synthesis of new protein and mRNA. TAM induction of apoptosis in MDA-231 cells depends primarily on protein synthesis. TAM-induced cytotoxicity and DNA damage appear to be explained in part by the induction of apoptosis.

引用

页码：238 / 245

页数：8

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