The antitumor agent PBT-1 directly targets HSP90 and hnRNP A2/B1 and inhibits lung adenocarcinoma growth and metastasis.
The antitumor agent PBT-1 directly targets HSP90 and hnRNP A2/B1 and inhibits lung adenocarcinoma growth and metastasis.
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DOI：
10.1021/jm401686b
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发表时间：
2014-02-13
影响因子：
7.3
通讯作者：
Yang PC
中科院分区：
文献类型：
--
作者：
Chen CY;Yang SC;Lee KH;Yang X;Wei LY;Chow LP;Wang TC;Hong TM;Lin JC;Kuan C;Yang PC
天然产物是目前可用的抗癌药物的主要来源。我们最近报道了基于菲的tylophorine衍生物-1 （PBT-1）可能是一种潜在的肺腺癌抗肿瘤药物。因此，我们研究了PBT-1的直接靶点及其在抑制肺腺癌中的作用。我们发现PBT-1在体外可降低Slug水平，抑制肺腺癌CL1-5细胞的迁移、侵袭和丝状足形成。此外，PBT-1对裸鼠皮下和原位异种移植的CL1-5细胞显示出体内抗肿瘤和抗转移活性。化学蛋白质组学表明，CL1-5细胞中热休克蛋白90 （HSP90）和异质核糖核蛋白A2/B1 （hnRNP A2/B1）结合PBT-1。抑制HSP90和hnRNP A2/B1可降低AKT的激活和Slug的表达。综上所述，这些发现表明PBT-1结合HSP90和/或hnRNP A2/B1，并通过影响Slug和akt介导的转移和肿瘤发生来启动抗肿瘤活性。
Natural products are the major sources of currently available anticancer drugs. We recently reported that phenanthrene-based tylophorine derivative-1 (PBT-1) may be a potential antitumor agent for lung adenocarcinoma. We therefore examined the direct targets of PBT-1 and their effects in inhibiting lung adenocarcinoma. We found that PBT-1 reduced the level of Slug and inhibits the migration, invasion, and filopodia formation of lung adenocarcinoma CL1-5 cells in vitro. In addition, PBT-1 displayed in vivo antitumor and antimetastasis activities against subcutaneous and orthotopic xenografts of CL1-5 cells in nude mice. Chemical proteomics showed that heat shock protein 90 (HSP90) and heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) bound PBT-1 in CL1-5 cells. Inhibition of HSP90 and hnRNP A2/B1 reduced the activation of AKT and Slug expression. Taken together, these findings suggest that PBT-1 binds to HSP90 and/or hnRNP A2/B1 and initiates antitumor activities by affecting Slug- and AKT-mediated metastasis and tumorigenesis.
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DOI：
10.1007/978-1-59745-416-2_24
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Yang, Ping
通讯作者：
Yang, Ping
影响因子：
15.9
作者：
Pan, Szu-Hua;Chao, Yu-Chih;Yang, Pan-Chyr
通讯作者：
Yang, Pan-Chyr
影响因子：
7.3
作者：
Lin JC;Yang SC;Hong TM;Yu SL;Shi Q;Wei L;Chen HY;Yang PC;Lee KH
通讯作者：
Lee KH
DOI：
10.1038/nrc2887
发表时间：
2010-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Trepel J;Mollapour M;Giaccone G;Neckers L
通讯作者：
Neckers L
影响因子：
11.5
作者：
Shih, JY;Tsai, MF;Yang, PC
通讯作者：
Yang, PC