A comparison of the antitumor activity of two triarylcyclopropyl antiestrogens (compounds 4d and 5c) on human breast cancer cells in culture.
A comparison of the antitumor activity of two triarylcyclopropyl antiestrogens (compounds 4d and 5c) on human breast cancer cells in culture.
复制标题
两种三芳基环丙基抗雌激素（化合物 4d 和 5c）对培养的人乳腺癌细胞的抗肿瘤活性比较。
DOI：
10.1097/00001813-199408000-00007
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发表时间：
1994
影响因子：
2.3
通讯作者：
Magarian,RA
中科院分区：
文献类型：
--
作者：
Jain,PT;Pento,JT;Magarian,RA
化合物4d ((E)和（Z)- 1,1 - dlchloro -2-[4-（苯氧基）-芳基]2,3 -ble（4-甲氧基苯基）环丙烷）和化合物5c (（2>)- 1,1 - dlchloro -2-[4-（苯氧基）-苯基]-2-(4-mothoxyphenyl)-3-苯基环丙烷）是一类新的三芳基环丙基化合物，已被证明是纯抗雌激素化合物。本研究检测了4d和5c对雌激素受体（ER）阳性MCF-7和ER阴性MDA-MB-231人乳腺癌细胞和A-549人肺癌细胞的抗增殖活性。化合物4d在10−13至10 ~ 6 M的浓度范围内以剂量相关的方式抑制MCF-7细胞的生长，而化合物5c在10−13至10−5 M的浓度范围内以剂量相关的方式抑制MCF-7细胞的生长。此外，两种化合物都没有改变MDA-MB-231或a -549细胞的生长。同时给药雌二醇可以逆转4d对MCF-7细胞的抗增殖活性，而5c对MCF-7细胞的抗增殖活性没有逆转作用。这两种化合物在MCF-7细胞中特异性结合内质网；而4d的相对结合活性是雌二醇的5倍，是5c的5000倍。采用扫描电镜观察4d和5c对MCF-7和MDA-MB-231细胞表面形态的影响。这两种化合物在浓度为10−6 M时，都降低了MCF-7细胞上微绒毛的密度，而在共注射雌二醇（10−8 M）时，这种情况被逆转。这些化合物没有改变er阴性MDA-MB-231细胞的表面形态。综上所述，本研究结果表明，化合物4d对乳腺癌细胞增殖的抑制作用强于5c，并提示化合物4d±苯基环上的极性甲氧基与内质网结合和内质网介导的抗肿瘤活性有关。此外，这些结果表明，其中一种或两种化合物可能对雌激素依赖性乳腺癌的治疗非常有效。
Compound 4d ((E)-and (Z)-1, 1-Dlchloro-2-[4-(benzyloxy)-phonyl] 2, 3-ble (4-methoxyphenyl) cyclopropane) and compound 5c ((2> 1, 1-Dlchloro-2-[4-(bonzyloxy)-phenyl]-2-(4-mothoxyphenyl)-3-phenylcyclopropane) are two members of a novel series of triarylcyclopropyl compounds which have been shown to be pure antiestro-gana. In the present study, the antiproliferative activity of 4d and 5c was examined on estrogen receptor (ER)-posltlve MCF-7 and ER-negatlva MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells. Compound 4d Inhibited the growth of MCF-7 cells In a dose-related manner over a concentration range of 10− 13 to 10∼ 6 M while compound 5c Inhibited MCF-7 cell growth in a dose-related manner over a concentration range of 10− 13 to 10− 5 M. Further, neither compound altered the growth of MDA-MB-231 or A-549 cells. Co-adminiatratlon of estradiol reversed the antiproliferative activity of 4d but not 5c on MCF-7 cells. Both compounds bound specifically to ER in MCF-7 cells; however, the relative binding activity of 4d was five times greater than estradiol and 5000 times greater than 5c. The influence of 4d and 5c on the cell surface morphology of MCF-7 and MDA-MB-231 cells was studied using scanning electron microacopy. Both compounds, at a concentration of 10− 6 M, reduced the density of microvilli on MCF-7 cells, which was reversed by co-admlnlatration of estradiol (10− 8 M). These compounds did not altar the cell surface morphology of ER-negatlve MDA-MB-231 cells. In conclusion, the results of this study indicate that compound 4d la mora potent than 5c as an Inhibitor of breast cancer cell proliferation and suggest that a polar methoxy group on the±phenyl ring of compound 4d contributes to ER binding and ER-medlated antitumor activity. Further, these results suggeet that one or both of these compounds may be highly effective in the treatment of estrogen-dependent breast cancer.