Antitumor activity of a novel antiestrogen (Analog II) on human breast cancer cells.
Antitumor activity of a novel antiestrogen (Analog II) on human breast cancer cells.
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新型抗雌激素（模拟 II）对人乳腺癌细胞的抗肿瘤活性。
DOI：
10.1097/00001813-199711000-00008
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发表时间：
1997
影响因子：
2.3
通讯作者：
Pento,JT
中科院分区：
文献类型：
--
作者：
Jain,PT;Rajah,TT;Pento,JT
类似物 II（1, 1-二氯-顺-2, 3-二芳基环丙烷）先前在小鼠中被证明是一种纯抗雌激素，现已检查其对培养的人乳腺癌细胞的潜在抗肿瘤活性。在这项研究中，Analog II 在 10− 11 至 10− 5 M 浓度范围内对雌激素受体 (ER) 阳性 MCF-7 人乳腺癌细胞的生长产生剂量相关的抗增殖作用。Analog II 增加了 MCF-7 细胞处于细胞周期 G 2/M 期的比例。此外，该化合物在 10− 9 至 10− 6 M 的浓度范围内抑制 ER 阴性 MDA-MB-231 人乳腺癌细胞的生长。使用扫描电子显微镜评估药物诱导的细胞形态变化，观察到 Analog II 减少了 MCF-7 和 MDA-MB-231 细胞上微绒毛的长度和密度。在雌二醇存在的情况下，Analog II 对 MCF-7 和 MDA-MB-231 细胞增殖和形态的影响不会逆转。此外，MCF-7细胞中雌激素依赖性基因的诱导并未被Analog II逆转。据观察，非特异性细胞毒性可能是模拟 II 诱导的 MCF-7 和 MDA-MB-231 细胞增殖抑制的部分原因。然而，该化合物的抗肿瘤活性被发现对人类乳腺癌细胞具有特异性，因为它不会改变非乳腺癌 A-549 人类肺癌细胞的增殖或活力。总之，这些结果表明Analog II是一种有效的抗肿瘤药物，在乳腺癌细胞中具有独特的抗肿瘤机制，可能有效治疗乳腺癌。
Analog II (1, 1-dichloro-cis-2, 3-diarylcyclopropane), previously shown to be a pure antiestrogen in mice, was examined for potential antitumor activity on human breast cancer cells in culture. In this study, Analog II produced a dose-related antiproliferative effect on the growth of estrogen receptor (ER)-positive MCF-7 human breast cancer cells over a concentration range of 10− 11 to 10− 5 M. Analog II increased the fraction of MCF-7 cells in the G 2/M phase of the cell cycle. Further, this compound inhibited the growth of ER-negative MDA-MB-231 human breast cancer cells over a concentration range of 10− 9 to 10− 6 M. Using scanning electron microscopy to evaluate drug-induced changes in cellular morphology, it was observed that Analog II decreased the length and density of microvilli on both MCF-7 and MDA-MB-231 cells. The effects of Analog II on MCF-7 and MDA-MB-231 cell proliferation and morphology were not reversed in the presence of estradiol. In addition, the induction of estrogen-dependent genes in MCF-7 cells was not reversed by Analog II. It was observed that non-specific cytotoxicity may be responsible for part of the Analog II-induced inhibition on MCF-7 and MDA-MB-231 cell proliferation. However, the antitumor activity of this compound was found to be specific to human breast cancer cells since it did not alter the proliferation or viability of non-breast A-549 human lung cancer cells. In conclusion, these results indicate that Analog II is a potent antitumor agent, has a unique antitumor mechanism in breast cancer cells and may be effective in the treatment of breast cancer.