Department of Obstetrics and Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT 06520, USA.
Cancer Biol Ther. 2009 Sep;8(18):1747-53. doi: 10.4161/cbt.8.18.9285. Epub 2009 Sep 17.
One of the major difficulties in the treatment of epithelial ovarian cancer (EOC) is the high rate of recurrent disease. This is thought to be due to the survival of a population of chemo-resistant cells within the tumor, the ovarian cancer stem cells (OCSCs), that are able to regenerate the tumor following chemotherapy. Therefore, the identification of a compund that can target the OCSCs is one of the main steps in improving overall survival of ovarian cancer patients. The objective of this study was to determine the effect of N-t-boc-Daidzein, a novel daidzain derivative, on OCSCs. The efficacy of this compound was evaluated in OCSC and mature ovarian cancer cell (mOCC) lines isolated from malignant ovarian cancer asicites. Cells were treated with increasing concentrations of N-t-boc-Daidzein (0.003-10 microM) and cell growth was monitored by "real time in vitro micro-imaging" using the IncuCyte system. Cell viability was measured using the CellTiter 96 Assay. Apoptosis was determined by Caspase-Glo 3/7, 8 and 9 assays. The components of the apoptotic cascade were characterized by western blot analysis. N-t-boc-Daidzein was able to significantly inhibit cell growth and decrease cell viability of OCSC as well as mOCC cells in a dose and time dependent maner. This effect was due to the induction of apoptosis, which is characterized by caspase activation, XIAP and AKT degradation, and mitochondrial depolarization. This study describes a novel compound that can target the OCSCs. These findings may provide vital aide in improving overall survival in patients with EOC.
上皮性卵巢癌（EOC）治疗的主要困难之一是复发性疾病的高发生率。这被认为是由于肿瘤内存在一群化疗耐药细胞，即卵巢癌干细胞（OCSCs），它们能够在化疗后再生肿瘤。因此，鉴定能够靶向 OCSCs 的化合物是提高卵巢癌患者总体生存率的主要步骤之一。本研究的目的是确定 N-t-boc-Daidzein（一种新型大豆苷元衍生物）对 OCSCs 的影响。该化合物的疗效在从恶性卵巢癌腹水中分离的 OCSC 和成熟卵巢癌细胞（mOCC）系中进行了评估。用递增浓度的 N-t-boc-Daidzein（0.003-10 μM）处理细胞，并使用 IncuCyte 系统通过“实时体外微成像”监测细胞生长。使用 CellTiter 96 测定法测量细胞活力。通过 Caspase-Glo 3/7、8 和 9 测定法测定细胞凋亡。通过 Western blot 分析来表征凋亡级联的组成部分。N-t-boc-Daidzein 能够以剂量和时间依赖的方式显著抑制 OCSC 以及 mOCC 细胞的生长并降低细胞活力。这种作用是由于诱导细胞凋亡所致，其特征是半胱天冬酶激活、XIAP 和 AKT 降解以及线粒体去极化。本研究描述了一种能够靶向 OCSCs 的新型化合物。这些发现可能为提高 EOC 患者的总体生存率提供重要帮助。
