Institute of Cancer Biology and Drug Screening, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.
Arch Pharm Res. 2009 Dec;32(12):1727-36. doi: 10.1007/s12272-009-2210-1. Epub 2010 Feb 17.
Piperazine is one of the heterocycles which are associated with diverse pharmacological activities. 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077) is a trisubstituted piperazine which contains a trimethoxybenzene ring and a benzhydrylpiperazine fragment, both of which can induce cell proliferation regression by different mechanisms. We have therefore examined the effects of PMS-1077 on Human Burkitt's lymphoma cells (Raji). The viability of Raji cells was determined by MTT assay and also assessed by trypan blue dye exclusion method. The results demonstrate that PMS-1077 can suppress the proliferation of Raji cells in a dose- and timedependent manner, while inhibit colony formation ability of Raji cells merely in a dose-dependent manner in vitro. Meanwhile, morphological changes were observed using fluorescence microscope. Flow cytometric analysis through PI stains showed that PMS-1077 blocked the growth of Raji cells in the G(0)/G(1) period, and induced apoptosis of Raji cells after 48 h of incubation. Cell apoptosis induced by PMS-1077 was further confirmed by staining with Annexin-V FITC and PI. Preliminary study by molecular docking suggests that PMS-1077 may inhibit tubulin polymerization. More experiments are in progress in our laboratory to reveal the mode of action of PMS-1077 in the induction of apoptosis of Raji cells.
哌嗪是一种杂环化合物,具有多种药理学活性。2-N,N-二乙基氨甲酰氧甲基-1-二苯甲基-4-(3,4,5-三甲氧基苯甲酰基)哌嗪盐酸盐(PMS-1077)是一种三取代哌嗪,含有一个三甲氧基苯环和一个苯并哌嗪片段,这两个片段都可以通过不同的机制诱导细胞增殖回归。因此,我们研究了 PMS-1077 对人 Burkitt 淋巴瘤细胞(Raji)的影响。Raji 细胞的活力通过 MTT 测定法和台盼蓝排斥试验进行评估。结果表明,PMS-1077 可以剂量和时间依赖性地抑制 Raji 细胞的增殖,而仅在体外以剂量依赖性方式抑制 Raji 细胞集落形成能力。同时,使用荧光显微镜观察到形态学变化。通过 PI 染色的流式细胞术分析显示,PMS-1077 将 Raji 细胞的生长阻滞在 G0/G1 期,并在孵育 48 小时后诱导 Raji 细胞凋亡。PMS-1077 诱导的细胞凋亡通过 Annexin-V FITC 和 PI 染色进一步得到证实。分子对接的初步研究表明,PMS-1077 可能抑制微管蛋白聚合。我们实验室正在进行更多的实验,以揭示 PMS-1077 在诱导 Raji 细胞凋亡中的作用方式。