Novel poly (ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells
文献类型：期刊论文
| 作者 | Wu, Xiaochen1; Li, Qiqi1; Zhang, Fan1; Wang, Lijun3; Wang, Jun1; Fan, Junting2; Di, Guohu4; Guo, Chuanlong1 |
| 刊名 | FOOD AND CHEMICAL TOXICOLOGY
 |
| 出版日期 | 2021 |
| 卷号 | 147页码:10 |
| ISSN号 | 0278-6915 |
| 关键词 | PARP inhibitor BRCA Pancreatic cancer |
| DOI | 10.1016/j.fct.2020.111892 |
| 通讯作者 | Guo, Chuanlong(guochuanlong@qust.edu.cn) |
| 英文摘要 | Poly (ADP-ribose) polymerases (PARPs) play a key role in DNA repair. In this study we designed a novel smallmolecular compound, (E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamide (DHC-1), which was a potent and selective PARP-1 inhibitor. DHC-1 selectively inhibited PARP-1 activity with an IC50 value of 41.12 +/- 13.28 nM. Cytotoxicity results showed that DHC-1 selectively inhibited the proliferation of BRCA1 -deficient breast cancer HCC-1937 and BRCA2-deficient pancreatic cancer Capan-1 cells. Mechanism studies found that DHC-1 stabilized PARP-1-DNA complexes and inhibited PAR formation in BRCA2(-/-) Capan-1 cells. Further experiments found that DHC-1 induced DNA double-strand damage in BRCA2(-/-) Capan-1 cells, which was demonstrated by accumulation of gamma-H2AX foci. Flow cytometry experiments revealed that DHC-1 induced G2/M phase arrest and activate mitochondrial-induced apoptotic pathways. Interestingly, we also found that DHC-1 enhanced cell proliferation inhibitory effect of oxaliplatin (OXA). The further in vivo nude mouse studies showed that DHC-1 inhibited the growth of Capan-1 xenografts and showed a similar mechanism to that in vitro. Collectively, our results demonstrate that DHC-1 may be an excellent candidate for treatment of BRCA-deficient pancreatic cancers. |
| 资助项目 | National Natural Science Foundation of China[81773586] |
| WOS研究方向 | Food Science & Technology ; Toxicology |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000604748100024 |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/169929]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 通讯作者 | Guo, Chuanlong |
| 作者单位 | 1.Qingdao Univ Sci & Technol, Coll Chem Engn, Dept Pharm, 53 Zhengzhou Rd, Qingdao 266042, Peoples R China 2.Nanjing Med Univ, Sch Pharm, Dept Pharmaceut Anal, Nanjing 211166, Peoples R China 3.Chinese Acad Sci, CAS Key Lab Expt Marine Biol, Ctr Ocean Megasci, Inst Oceanol, 7 Nanhai Rd, Qingdao 266071, Peoples R China 4.Qingdao Univ, Sch Basic Med, 308 Ningxia Rd, Qingdao 266071, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Xiaochen,Li, Qiqi,Zhang, Fan,et al. Novel poly (ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells[J]. FOOD AND CHEMICAL TOXICOLOGY,2021,147:10. |
| APA | Wu, Xiaochen.,Li, Qiqi.,Zhang, Fan.,Wang, Lijun.,Wang, Jun.,...&Guo, Chuanlong.(2021).Novel poly (ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells.FOOD AND CHEMICAL TOXICOLOGY,147,10. |
| MLA | Wu, Xiaochen,et al."Novel poly (ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells".FOOD AND CHEMICAL TOXICOLOGY 147(2021):10. |
入库方式： OAI收割
来源：海洋研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。