A new arylbenzofuran derivative functions as an anti-tumour agent by inducing DNA damage and inhibiting PARP activity
文献类型：期刊论文
| 作者 | Chen, Hongbo1,6,7; Zeng, Xiaobin1,6,7,8; Gao, Chunmei1,6,7; Ming, Pinghong2; Zhang, Jianping3; Guo, Caiping3; Zhou, Lanzhen3; Lu, Yin5; Wang, Lijun1,6,7; Huang, Laiqiang1,6,7 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2015-06-04 |
| 卷号 | 5 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep10893 |
| 文献子类 | Article |
| 英文摘要 | We previously reported that 7-hydroxy-5, 4'-dimethoxy-2-arylbenzofuran (HDAB) purified from Livistona chinensis is a key active agent. The present study investigated the function and molecular mechanism of HDAB. HDAB treatment of cervical cancer cells resulted in S phase arrest and apoptosis, together with cyclin A2 and CDK2 upregulation. Cyclin A2 siRNA and a CDK inhibitor efficiently relieved S phase arrest but increased the apoptosis rate. Mechanistic studies revealed that HDAB treatment significantly increased DNA strand breaks in an alkaline comet assay and induced ATM, CHK1, CHK2 and H2A. X phosphorylation. Wortmannin (a broad inhibitor of PIKKs) and CGK733 (a specific ATM inhibitor), but not LY294002 (a phosphatidylinositol 3-kinase inhibitor) or NU7026 (a DNA-PK specific inhibitor), prevented H2A. X phosphorylation and. H2A. X-positive foci formation in the nuclei, reversed S phase arrest and promoted the HDAB-induced apoptosis, suggesting that HDAB is a DNA damaging agent that can activate the ATM-dependent DNA repair response, thereby contributing to cell cycle arrest. In addition, molecular docking and in vitro activity assays revealed that HDAB can correctly dock into the hydrophobic pocket of PARP-1 and suppress PARP-1 ADP-ribosylation activity. Thus, the results indicated that HDAB can function as an anti-cancer agent by inducing DNA damage and inhibiting PARP activity. |
| WOS关键词 | DEPENDENT PROTEIN-KINASE ; ADP-RIBOSE POLYMERASE ; LUNG-CANCER CELLS ; POLY(ADP-RIBOSE) POLYMERASE ; GENOTOXIC STRESS ; HPV TYPES ; S-PHASE ; APOPTOSIS ; ATM ; SENSITIVITY |
| 资助项目 | Chinese National Natural Science Foundation[21372141] ; Chinese National Natural Science Foundation[31270019] ; Chinese National Natural Science Foundation[51203085] ; Guangdong Natural Science Foundation[2014A030313758] ; Guangdong Natural Science Foundation[2014A030306036] ; Guangdong Natural Science Foundation[2014A030310365] ; Ministry of Education of China[20120002120020] ; Science, Technology & Innovation Commission of Shenzhen Municipality[JCYJ20120616213411826] ; Science, Technology & Innovation Commission of Shenzhen Municipality[JCYJ20140417115840285] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000363618600001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276496]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Huang, Laiqiang |
| 作者单位 | 1.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China; 2.Zhuhai Peoples Hosp, Clin Lab, Zhuhai 519000, Peoples R China; 3.Shenzhen Weiguang Biol Prod Co Ltd, Shenzhen 518107, Peoples R China; 4.Guangdong Pharmaceut Univ, Coll Pharm, Guangzhou 510006, Guangdong, Peoples R China 5.Shanghai Inst Mat Med, DDDC, Shanghai 201203, Peoples R China; 6.Tsinghua Univ, Shenzhen Grad Sch, Shenzhen Key Lab Gene & Antibody Therapy, Minist Prov Jointly Constructed Base State Key La, Shenzhen 518055, Peoples R China; 7.Tsinghua Univ, Shenzhen Grad Sch, Div Life & Hlth Sci, Shenzhen 518055, Peoples R China; 8.Guangdong Med Coll, Guangdong Key Lab Res & Dev Nat Drugs, Zhanjiang 524023, Guangdong, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Hongbo,Zeng, Xiaobin,Gao, Chunmei,et al. A new arylbenzofuran derivative functions as an anti-tumour agent by inducing DNA damage and inhibiting PARP activity[J]. SCIENTIFIC REPORTS,2015,5. |
| APA | Chen, Hongbo.,Zeng, Xiaobin.,Gao, Chunmei.,Ming, Pinghong.,Zhang, Jianping.,...&Mei, Lin.(2015).A new arylbenzofuran derivative functions as an anti-tumour agent by inducing DNA damage and inhibiting PARP activity.SCIENTIFIC REPORTS,5. |
| MLA | Chen, Hongbo,et al."A new arylbenzofuran derivative functions as an anti-tumour agent by inducing DNA damage and inhibiting PARP activity".SCIENTIFIC REPORTS 5(2015). |
入库方式： OAI收割
来源：上海药物研究所
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