Su Shan, Cheng Xinlai, Wink Michael
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
J Pharm Pharmacol. 2015 Sep;67(9):1316-23. doi: 10.1111/jphp.12426. Epub 2015 Apr 29.
Arctigenin and matairesinol possess a diversity of bioactivities. Here we investigated the cytotoxicity of arctigenin and matairesinol against a T-cell lymphoma cell line CCRF-CEM and the underlying mechanisms that have not been explored before.
The cytotoxic activity was investigated using MTT assay. The cell cycle arrest and reactive oxygen species (ROS) accumulation were determined by flow cytometric analysis. The apoptosis induction was assessed using Annexin V/Propidium Iodide assay. The gene quantification analysis was measured through real-time polymerase chain reaction.
Arctigenin and matairesinol exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 μm and 4.27 ± 0.41 μm, respectively. In addition, both lignans arrest CCRF-CEM cells in the S phase. Furthermore, they could induce apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Interestingly, the lignans differentially regulated the expression of several key genes involved in apoptosis pathways, including Bax, Bad and caspase-9. Moreover, both lignans could increase ROS levels in CCRF-CEM cells.
Our study provides an insight into the potential of arctigenin and matairesinol as good candidates for the development of novel agents against T-cell lymphoma.
牛蒡子苷元和罗汉松脂素具有多种生物活性。在此,我们研究了牛蒡子苷元和罗汉松脂素对T细胞淋巴瘤细胞系CCRF-CEM的细胞毒性以及此前未被探索的潜在机制。
采用MTT法研究细胞毒性活性。通过流式细胞术分析确定细胞周期阻滞和活性氧(ROS)积累情况。使用膜联蛋白V/碘化丙啶法评估细胞凋亡诱导情况。通过实时聚合酶链反应进行基因定量分析。
用牛蒡子苷元和罗汉松脂素处理CCRF-CEM细胞72小时后,它们表现出显著的抗增殖活性,IC50值分别为1.21±0.15μm和4.27±0.41μm。此外,两种木脂素均使CCRF-CEM细胞停滞于S期。而且,它们能以浓度和时间依赖性方式诱导CCRF-CEM细胞凋亡。有趣的是,这两种木脂素对凋亡途径中几个关键基因的表达有不同调节作用,包括Bax、Bad和caspase-9。此外,两种木脂素均能提高CCRF-CEM细胞中的ROS水平。
我们的研究为牛蒡子苷元和罗汉松脂素作为开发抗T细胞淋巴瘤新型药物的良好候选物的潜力提供了见解。