School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
Int J Mol Sci. 2017 Sep 21;18(10):2025. doi: 10.3390/ijms18102025.
Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL), an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. Furthermore, the expression of cleaved PARP, cleaved caspase-3, Bax/Bcl-2 ratio, LC3B-II, and Beclin-1 levels were increased in western blot analysis. To clarify the role of autophagy and apoptosis in the effect of ISL, we used the autophagy inhibitor-3-methyladenine (3-MA) to attenuate the punctate fluorescence staining pattern of the p62/sequestosome 1 (SQSTM1, red fluorescence) and LC3 (green fluorescence) proteins after ISL treatment, and 3-MA inhibited the cytotoxicity of ISL. These findings provide new information about the link between ISL-induced autophagy and apoptosis and suggest that ISL is a candidate agent for the treatment of human ovarian cancer.
卵巢癌是最常见的妇科恶性肿瘤之一,晚期患者预后较差。甘草中的活性黄酮类成分异甘草素(ISL)先前已被证明具有抗氧化、抗炎和肿瘤抑制作用。在这项研究中,我们使用人卵巢癌细胞系 OVCAR5 和 ES-2 作为模型系统,在体外研究了 ISL 对人卵巢癌的抗肿瘤作用。结果表明,ISL 呈浓度和时间依赖性地显著抑制癌细胞活力。流式细胞术分析表明,ISL 诱导 G2/M 期阻滞。此外,Western blot 分析表明,裂解的 PARP、裂解的 caspase-3、Bax/Bcl-2 比值、LC3B-II 和 Beclin-1 水平增加。为了阐明自噬和细胞凋亡在 ISL 作用中的作用,我们使用自噬抑制剂 3-甲基腺嘌呤(3-MA)减弱 ISL 处理后 p62/自噬体 1(SQSTM1,红色荧光)和 LC3(绿色荧光)蛋白的点状荧光染色模式,并且 3-MA 抑制了 ISL 的细胞毒性。这些发现为 ISL 诱导的自噬和细胞凋亡之间的联系提供了新的信息,并表明 ISL 是治疗人类卵巢癌的候选药物。