Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC.
Oncol Rep. 2012 Dec;28(6):2069-76. doi: 10.3892/or.2012.2029. Epub 2012 Sep 12.
Leukemia, one of the causes of cancer-related death in humans, is an aggressive malignancy via the rapid growth of abnormal white blood cells. The aim of this study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra, has been proven to induce cytotoxic effects in many cancer cell lines. In the current study, we investigated the effects of GA in mouse leukemia cells in vitro. The results indicated that GA induced morphological changes, G0/G1 phase arrest, apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast microscopy, DAPI-staining, flow cytometry and comet assay. The results from the flow cytometric assay showed that GA increased ROS levels, reduced the mitochondrial membrane potential (ΔΨm) and stimulated caspase-3 activity in WEHI-3 cells. GA regulated the intrinsic and extrinsic apoptosis-associated protein expression which was determined by western blotting. In addition, endoplasmic reticulum (ER) stress responses were observed in GA-treated WEHI-3 cells. GA promoted the trafficking of apoptosis-inducing factor (AIF), cytochrome c and endonuclease G (Endo G) in WEHI-3 cells. Based on this evidence, GA-triggered apoptosis occurs through the death receptor, mitochondria-mediated and ER stress multiple signaling pathways.
白血病是人类癌症相关死亡的原因之一，是一种通过异常白细胞快速生长的侵袭性恶性肿瘤。本研究旨在确定甘草酸（GA）对 WEHI-3 小鼠白血病细胞系的抗白血病作用。GA 是甘草中的一种活性化合物，已被证明在许多癌细胞系中具有细胞毒性作用。在本研究中，我们研究了 GA 在体外对小鼠白血病细胞的影响。结果表明，GA 通过相差显微镜、DAPI 染色、流式细胞术和彗星试验诱导 WEHI-3 细胞发生形态变化、G0/G1 期阻滞、凋亡和 DNA 损伤。流式细胞术结果表明，GA 增加了 WEHI-3 细胞中的 ROS 水平，降低了线粒体膜电位（ΔΨm），并刺激了 caspase-3 活性。GA 通过 Western blot 确定了内在和外在凋亡相关蛋白的表达。此外，还观察到 GA 处理的 WEHI-3 细胞中的内质网（ER）应激反应。GA 促进了凋亡诱导因子（AIF）、细胞色素 c 和内切核酸酶 G（Endo G）在 WEHI-3 细胞中的运输。基于这些证据，GA 触发的细胞凋亡通过死亡受体、线粒体介导和 ER 应激多种信号通路发生。
