Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function
Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function
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Pharicin A 是一种新型天然对映贝壳杉烯二萜类化合物，通过干扰 BubR1 功能诱导癌细胞有丝分裂停滞和有丝分裂灾难
DOI：
10.4161/cc.9.14.12406
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发表时间：
2010-07
期刊：
影响因子：
4.3
通讯作者：
Xiao, Wei-Lie
中科院分区：
文献类型：
--
作者：
Chen, Guo-Qiang;Huang, Ying;Sun, Han-Dong;Lin, Qi-Shan;Wu, Ying-Li;Dai, Wei;Zhao, Yong;Xu, Han-Zhang;Xiao, Wei-Lie
在这项研究中，我们报告了一个新的ent-kaurene二萜称为pharicin A，这最初是从干燥香茶菜，一种多年生灌木，经常在中国民间医药用于肿瘤治疗分离的功能特性。Pharicin A诱导白血病和实体瘤衍生细胞的有丝分裂停滞，通过其形态、DNA含量和有丝分裂标记物分析鉴定。Pharicin A诱导的有丝分裂阻滞与染色体未对齐、BubR 1异常定位和纺锤体检查点激活失调有关。Pharicin A在体外直接与BubR 1结合，这与体内姐妹染色单体过早分离相关。Pharicin A还诱导紫杉醇抗性Jurkat和U2 OS细胞中的有丝分裂停滞。结合，我们的研究强烈表明，pharicin A代表了一类新的小分子化合物，能够干扰有丝分裂进程和启动有丝分裂灾难，值得进一步的临床前和临床研究癌症药物开发。
In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon xerophilus, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content, and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization, and deregulated spindle checkpoint activation. Pharicin A directly binds to BubR1 in vitro, which is correlated with premature sister chromatid separation in vivo. Pharicin A also induces mitotic arrest in paclitaxel-resistant Jurkat and U2OS cells. Combined, our study strongly suggests that pharicin A represents a novel class of small molecule compounds capable of perturbing mitotic progression and initiating mitotic catastrophe, which merits further preclinical and clinical investigations for cancer drug development.
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DOI：
10.1016/s1040-8428(02)00105-1
发表时间：
2002-12
期刊：
Critical reviews in oncology/hematology
影响因子：
--
作者：
H. Lück;H. Roché
通讯作者：
H. Lück;H. Roché
影响因子：
9.8
作者：
McGuinness BE;Hirota T;Kudo NR;Peters JM;Nasmyth K
通讯作者：
Nasmyth K
影响因子：
4.8
作者：
Bin, OY;Pan, HQ;Dai, W
通讯作者：
Dai, W
影响因子：
8
作者：
Bin, OY;Li, WQ;Dai, W
通讯作者：
Dai, W
影响因子：
64.5
作者：
Mao, YH;Abrieu, A;Cleveland, DW
通讯作者：
Cleveland, DW