beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases.
beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases.
复制标题
beta-lapachone 通过调节 Bcl-2 家族和激活 caspase 来诱导膀胱癌细胞的生长抑制和凋亡。
作者：
J. I. Lee;D. Choi;H. Chung;H. Seo;H. Woo;B. Choi;Y. H. Choi
目的
研究从拉帕乔树皮中提取的醌类物质--β-拉帕乔酮（beta-lapachone）诱导细胞凋亡的分子机制。
材料和方法
本研究在人膀胱癌T24细胞系上进行。用台盼蓝拒染法测定细胞活力，用DAPI染色和琼脂糖凝胶电泳进行细胞凋亡定量评估。流式细胞术分析、RT-PCR和Western blot分析、比色法检测caspase活性。
结果
结果表明，在微摩尔浓度范围内，β-拉帕醌通过诱导T24细胞凋亡抑制T24细胞活力，凋亡小体的形成和DNA片段化可证明这一点。用β-拉帕醌处理T24细胞导致Bcl-2表达下调和Bax表达上调。β-拉帕酮诱导的细胞凋亡还与caspase-3和caspase-9的激活、IAP表达的抑制以及聚（ADP-核糖）聚合酶、磷脂酶C-γ 1和β-连环蛋白的降解相关。同时，Fas和FasL水平在用β-拉帕醌处理后以浓度依赖性方式被抑制。
结论
β-拉帕醌诱导的T24细胞凋亡至少部分是由细胞信号传导途径介导的。
AIM
To study in vitro the molecular mechanism of apoptosis caused by beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae).
MATERIALS AND METHODS
The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion method, apoptosis quantitative estimation - by DAPI staining and agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT-PCR and Western blot analysis, colorimetric assay of caspase activity were applied as well.
RESULTS
It was found that in micromolar range of concentrations beta-lapachone inhibited the viability of T24 cells by inducing apoptosis, which could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment of T24 cells with beta-lapachone resulted in a down-regulation of Bcl-2 expression and up-regulation of Bax expression. beta-lapachone-induced apoptosis was also associated with activation of caspase-3 and caspase-9, inhibition of IAP expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C-gamma1 and beta-catenin proteins. At the same time Fas and FasL levels were inhibited upon treatment with beta-lapachone in a concentration-dependent manner.
CONCLUSION
beta-lapachone-induced apoptosis in T24 cells is mediated, at least in part, by the mitochondrial-signaling pathway.
通过拓扑异构酶 I 的激活剂 β-拉帕酮抑制人类肿瘤细胞中潜在致命的 DNA 损伤修复。
影响因子：
11.2
作者：
Boothman,DA;Trask,DK;Pardee,AB
通讯作者：
Pardee,AB
beta-Lapachone 是一种新型 DNA 拓扑异构酶 I 抑制剂，其作用方式与喜树碱不同。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Li,CJ;Averboukh,L;Pardee,AB
通讯作者：
Pardee,AB
β-拉帕酮和相关萘醌诱导 DNA 拓扑异构酶 II 介导的 DNA 切割。
影响因子：
11.2
作者：
Frydman,B;Marton,LJ;Sun,JS;Neder,K;Witiak,DT;Liu,AA;Wang,HM;Mao,Y;Wu,HY;Sanders,MM;Liu,LF
通讯作者：
Liu,LF