Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Korea.
Department of Chemistry, College of Natural Sciences, Salale University, Fitche, P.O. Box 245, Ethiopia.
Molecules. 2020 Jan 3;25(1):207. doi: 10.3390/molecules25010207.
The seeds of are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3',4'-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.
在埃塞俄比亚， 种子被用于捕鱼、农药和民间医学。在这里，评估了从 中分离出的异黄酮对人卵巢癌细胞的抗癌作用。我们发现，异黄酮 ferrugone 和 6,7-二甲氧基-3',4'-亚甲二氧基-8-(3,3-二甲基烯丙基）异黄酮（DMI）对人卵巢癌细胞 A2780 和 SKOV3 具有很强的细胞毒性作用。Ferrugone 和 DMI 处理以剂量依赖的方式增加 A2780 细胞中的亚 G1 细胞群。Ferrugone 和 DMI 的细胞毒性活性与诱导细胞凋亡有关，这表现为 Annexin V 阳性细胞的增加。广谱半胱氨酸天冬氨酸蛋白酶（caspase）抑制剂 Z-VAD-fmk 和 caspase-3 抑制剂 z-DEVD-fmk 显著逆转了 ferrugone 和 DMI 诱导的凋亡，表明异黄酮刺激的细胞死亡是由 caspase-3 依赖性凋亡介导的。此外，发现 ferrugone 诱导的凋亡依赖于 caspase-8，而 DMI 诱导的凋亡依赖于 caspase-9。值得注意的是，DMI 而非 ferrugone 增加了细胞内活性氧（ROS）的水平，抗氧化剂 N-乙酰-L-半胱氨酸（NAC）减弱了 DMI 的促凋亡活性。这些数据表明，DMI 通过 ROS 产生诱导人卵巢癌细胞内在途径的凋亡细胞死亡，而 ferrugone 刺激人卵巢癌细胞中的外在途径。
