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The natural product Aristolactam AIIIa as a new ligand targeting the polo-box domain of polo-like kinase 1 potently inhibits cancer cell proliferation

文献类型：期刊论文

作者Li, Li2; Wang, Xu1; Chen, Jing1; Ding, Hong1; Zhang, Yu1; Hu, Tian-cen1; Hu, Li-hong1; Jiang, Hua-liang1,2; Shen, Xu1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2009-10
卷号30期号:10页码:1443-1453
关键词antitumor drugs Aristolactam AIIIa Polo-box domain Polo-like kinase 1 inhibitor
ISSN号1671-4083
DOI10.1038/aps.2009.141
文献子类Article
英文摘要Aim: To search for novel inhibitors of human polo-like kinase 1 (Plk1), which plays important roles in various aspects of mitotic progression and is believed as a promising anti-cancer drug target, and further investigate the potential inhibition mechanism of active compounds against Plk1, thus developing potent anti-tumor lead compounds. Methods: Surface plasmon resonance (SPR) technology-based assay and enzymatic inhibition assay were used to screen Plk1 inhibitors. Sulphorhodamine B (SRB)-based assay, flow cytometry, confocal microscopy and Western blotting were used to further identify the potent Plk1 inhibitor. To investigate the inhibitory mechanism of the active compound against Plk1, enzymatic inhibition assay, SPR and yeast two-hybrid technology-based assays were used. Results: Aristolactam AIIIa was identified as a new type of Plk1 inhibitors, targeting the Polo Box domain (PBD) which is another efficient tactic for exploring Plk1 inhibitors. Further studies indicated that it could block the proliferations of HeLa, A549, HGC and the HCT-8/V cells (clinical Navelbine-resistant cancer cell), induce mitotic arrest of HeLa cells at G(2)/M phase with spindle abnormalities and promote apoptosis in HeLa cells. The results from SPR and yeast two-hybrid technology-based assays suggested that it could target both the catalytic domain of Plk1 (CD) and PBD and enhance the CD/PBD interaction. Conclusion: Our current work is expected to shed light on the potential anti-tumor mechanism of Aristolactam AIIIa, and this natural product might be possibly used as a lead compound for further developing anti-tumor drugs.
WOS关键词SERINE/THREONINE KINASE ; PLK1 ; IDENTIFICATION ; POLO-LIKE-KINASE-1 ; DIOXOAPORPHINES ; PHOSPHORYLATION ; SCYTONEMIN ; APOPTOSIS ; THERAPY ; MITOSIS
资助项目State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[30890044] ; Shanghai Science and Technology Commission[0811141013] ; Chinese Academy of Sciences[SIMM0709QN-19]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:3739976
WOS记录号WOS:000270733600009
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/279106]  
专题药物安全性评价中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
上海中药现代化研究中心
通讯作者Chen, Jing
作者单位1.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式
GB/T 7714		 Li, Li,Wang, Xu,Chen, Jing,et al. The natural product Aristolactam AIIIa as a new ligand targeting the polo-box domain of polo-like kinase 1 potently inhibits cancer cell proliferation[J]. ACTA PHARMACOLOGICA SINICA,2009,30(10):1443-1453.
APA Li, Li.,Wang, Xu.,Chen, Jing.,Ding, Hong.,Zhang, Yu.,...&Shen, Xu.(2009).The natural product Aristolactam AIIIa as a new ligand targeting the polo-box domain of polo-like kinase 1 potently inhibits cancer cell proliferation.ACTA PHARMACOLOGICA SINICA,30(10),1443-1453.
MLA Li, Li,et al."The natural product Aristolactam AIIIa as a new ligand targeting the polo-box domain of polo-like kinase 1 potently inhibits cancer cell proliferation".ACTA PHARMACOLOGICA SINICA 30.10(2009):1443-1453.

入库方式： OAI收割

来源：上海药物研究所

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