Liu Hong-li, Chen Yan, Cui Guo-hui, Wu Qiu-ling, Chen Wei-hua, He Jing
Institute of Hematology, Union Hospital, Tongdi Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Zhong Liu Za Zhi. 2007 Mar;29(3):176-80.
To investigate the anticancer effects and molecular mechanism of deguelin on human Burkitt's lymphoma Daudi cells in vitro and compare the cytotoxicity of deguelin on Daudi cells and human peripheral blood monocular cells (HPBMC).
The effects of deguelin on the growth of Daudi cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5 diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was assessed through Hoechst 33258 staining and annexin V/PI double-labeled cytometry. The effect of deguelin on the cell cycle of Daudi cells was studied by propidium iodide method. The expressions of cyclin D1 and pRb were checked by Western blot.
The proliferation of Daudi cells was decreased in deguelin-treated group with a 24 h IC50 value of 51. 55 nmol/L. Deguelin induced Daudi cells apoptosis in a time- and dose-dependent manner. Daudi cells treated with deguelin showed an increase of G0/G1 phase and decrease of S phase. The Daudi cells treated with 0, 5, 10, 20, 40 nmol/L deguelin for 24 h, showed an increased Go/G, phase from 37.34% to 56.56% , whereas decreased S phase from 37.72% to 21.36%, respectively. PBMC was less sensitive to the cytotoxic effect of deguelin than Daudi cells. The expression of cyclin D1 and pRb protein were decreased in Daudi cells treated with deguelin.
Deguelin can inhibit the proliferation of Daudi cells by regulating the cell cycle that arrest cells at G0/G1 phase and inducing apoptosis. Moreover, deguelin demonstrats low toxicity in PBMC but selectively induces apoptosis of Daudi cells. The antitumor effects of deguelin may be related to down-regulation of the expression of cyclin D1 and pRb protein.
研究鱼藤素对人伯基特淋巴瘤Daudi细胞的体外抗癌作用及其分子机制,并比较鱼藤素对Daudi细胞和人外周血单个核细胞(HPBMC)的细胞毒性。
采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四氮唑溴盐(MTT)法研究鱼藤素对Daudi细胞生长的影响。通过Hoechst 33258染色和膜联蛋白V/碘化丙啶双标记流式细胞术评估细胞凋亡情况。采用碘化丙啶法研究鱼藤素对Daudi细胞周期的影响。通过蛋白质免疫印迹法检测细胞周期蛋白D1(cyclin D1)和磷酸化视网膜母细胞瘤蛋白(pRb)的表达。
鱼藤素处理组Daudi细胞的增殖受到抑制,24小时半数抑制浓度(IC50)值为51.55纳摩尔/升。鱼藤素以时间和剂量依赖性方式诱导Daudi细胞凋亡。经鱼藤素处理的Daudi细胞G0/G1期增加,S期减少。用0、5、10、20、40纳摩尔/升鱼藤素处理Daudi细胞24小时后,G0/G1期从37.34%增加到56.56%,而S期从37.72%分别降至21.36%。PBMC对鱼藤素细胞毒性的敏感性低于Daudi细胞。鱼藤素处理的Daudi细胞中cyclin D1和pRb蛋白的表达降低。
鱼藤素可通过调节细胞周期,使细胞停滞于G0/G1期并诱导凋亡,从而抑制Daudi细胞的增殖。此外,鱼藤素对PBMC毒性较低,但能选择性地诱导Daudi细胞凋亡。鱼藤素的抗肿瘤作用可能与下调cyclin D1和pRb蛋白的表达有关。