Department of Environmental Health Sciences, University Medical Center Freiburg, Breisacher Strasse 115b, 79106 Freiburg, Germany.
Phytother Res. 2013 Jul;27(7):1036-41. doi: 10.1002/ptr.4798. Epub 2012 Sep 5.
In the present study we analysed the effects of isothiocyanates (ITCs)--plant-derived sulphur-containing constituents known for their potential chemotherapeutic activity--on growth inhibition and programmed death in primary ovarian carcinoma cells from ascites of human patients. Twenty-four hour exposure of carcinoma cells to 5-50 μM erucin or benzyl ITC led to a concentration-dependent viability loss, as determined by erytrosin B cell staining. This concurred with an increase in internucleosomal DNA fragmentation, mitochondrial membrane depolarization and downregulation of Akt as indicator for apoptosis induction. Cell accumulation at the G2/M phase was evident after 48 h of erucin treatment. Telomerase, a selective target of cancer cells, was suppressed by erucin. Although pre-treatment of cells with the thiol antioxidant N-acetylcysteine could completely prevent initialization of the apoptotic process, it failed to abolish ITC-mediated telomerase suppression. Taken together, in our study, ITC exerted comparable cytotoxic efficacy against primary ovarian cancer cells as reported for corresponding cell lines. The clinical significance of this observation should be addressed in future studies and the role of telomerase further investigated.
在本研究中，我们分析了异硫氰酸酯（ITC） - 植物衍生的含硫成分，因其潜在的化疗活性而闻名 - 对人卵巢癌患者腹水来源的原发性卵巢癌细胞生长抑制和程序性死亡的影响。用 5-50 μM 葡萄糖胺或苄基 ITC 处理癌细胞 24 小时，导致细胞活力丧失，这与细胞内 DNA 片段化、线粒体膜去极化和 Akt 下调增加相一致，Akt 是诱导细胞凋亡的指标。用葡萄糖胺处理 48 小时后，细胞明显积累在 G2/M 期。端粒酶是癌细胞的选择性靶点，被葡萄糖胺抑制。尽管用硫醇抗氧化剂 N-乙酰半胱氨酸预处理细胞可以完全阻止凋亡过程的启动，但它不能消除 ITC 介导的端粒酶抑制。总之，在我们的研究中，ITC 对原发性卵巢癌细胞的细胞毒性作用与相应的细胞系相似。未来的研究应探讨这一观察结果的临床意义，并进一步研究端粒酶的作用。
