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4-(甲硫基)丁基异硫氰酸酯抑制不同受体状态的乳腺癌细胞的增殖。

4-(Methylthio)butyl isothiocyanate inhibits the proliferation of breast cancer cells with different receptor status.

机构信息

Department of Medical Biology and Genetics, University of Gdańsk, Gdańsk, Poland.

Department of Medical Biology and Genetics, University of Gdańsk, Gdańsk, Poland.

出版信息

Pharmacol Rep. 2017 Oct;69(5):1059-1066. doi: 10.1016/j.pharep.2017.04.014. Epub 2017 Apr 23.

Abstract

BACKGROUND

Epidemiological studies indicate that the consumption of Brassicaceae plants, a rich source of biologically active isothiocyanates (ITCs), may effectively reduce cancer risk. In the current study, we evaluated the anticancer potential of 4-(methylthio)butyl ITC (erucin, ERN) against three phenotypically different breast cancer cell lines: MDA-MB-231, SKBR-3 and T47D.

METHODS

The effect of ERN on the viability of breast cancer cells was evaluated using sulforhodamine B and clonogenic assays, and acridine orange/ethidium bromide staining. Cell cycle was investigated using flow cytometry. The status of signaling molecules was examined by western blot analysis.

RESULTS

ERN decreased the viability of all tested cancer cell lines in a concentration-dependent manner; this effect was much weaker in normal breast cells (MCF-10A). ERN induced cell cycle arrest in the G2/M phase, down-regulated the phosphorylation of S6 ribosomal protein in all tested breast cancer cell lines, and reduced HER2 receptor levels in SKBR-3 cells. A 24-h treatment with lower concentrations of ERN (5-20μM) induced apoptosis; higher ERN concentrations (40μM) induced necrosis. The latter also irreversibly inhibited the proliferative potential of cancer cells.

CONCLUSION

ERN effectively inhibits proliferation of breast cancer cells irrespectively of their receptor status.

摘要

背景

流行病学研究表明,十字花科植物的消费,生物活性异硫氰酸酯(ITC)的丰富来源,可能有效地降低癌症的风险。在目前的研究中,我们评估了 4-(甲基硫代)丁基 ITC(萝卜硫素,ERN)对三种表型不同的乳腺癌细胞系:MDA-MB-231、SKBR-3 和 T47D 的抗癌潜力。

方法

用磺酰罗丹明 B 和集落形成试验和吖啶橙/溴化乙锭染色法评估 ERN 对乳腺癌细胞活力的影响。用流式细胞术研究细胞周期。用 Western blot 分析检查信号分子的状态。

结果

ERN 以浓度依赖性方式降低所有测试的癌细胞系的活力; 在正常乳腺细胞(MCF-10A)中,这种作用要弱得多。ERN 在所有测试的乳腺癌细胞系中诱导细胞周期停滞在 G2/M 期,下调 S6 核糖体蛋白的磷酸化,并降低 SKBR-3 细胞中的 HER2 受体水平。用较低浓度的 ERN(5-20μM)处理 24 小时诱导细胞凋亡; 更高浓度的 ERN(40μM)诱导坏死。后者还不可逆地抑制了癌细胞的增殖潜力。

结论

ERN 有效地抑制了乳腺癌细胞的增殖,而与受体状态无关。

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