Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate
文献类型：期刊论文
| 作者 | Nie, Jing3; Hu, Wentao3; Pei, Hailong3; Zhou, Guangming3 ; Chen, Weiqiang2; Hei, Tom K.1; Li, Bingyan3; Pan, Shuxian3; Ding, Jiahan3; Guo, Ziyang3
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 2019-05-01 |
| 卷号 | 93期号:5页码:874-882 |
| 关键词 | autophagy cell cycle arrest chloroquine lung cancer primary mouse lung tumor |
| ISSN号 | 1747-0277 |
| DOI | 10.1111/cbdd.13477 |
| 通讯作者 | Chen, Weiqiang(chenwq7315@impcas.ac.cn) ; Zhou, Guangming(gmzhou@suda.edu.cn) |
| 英文摘要 | Aim Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy. Methods In vitro cultured non-small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B-blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy. Results Compared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO-3 was the most effective. The LD50 for CQBTO-3 was 21 mu M in A549 cells and 21.5 mu M in Calu-1 cells, which was lower than that of CQBTO-2 or CQBTO-1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO-3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO-3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation. Conclusion CQBTO-3 is a potential chemical compound for lung cancer treatment. |
| WOS关键词 | CANCER-CELLS ; AUTOPHAGY ; THERAPY ; RESISTANCE ; APOPTOSIS ; MODEL ; DRUG |
| 资助项目 | National Natural Science Foundations of China[81602794] ; National Natural Science Foundations of China[81773463] ; National Natural Science Foundations of China[81673151] ; China Postdoctoral Science Foundation[2017T100399] ; Natural Science Foundations of Jiangsu Province[BK20160334] ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000468814500017 |
| 出版者 | WILEY |
| 资助机构 | National Natural Science Foundations of China ; China Postdoctoral Science Foundation ; Natural Science Foundations of Jiangsu Province ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) |
| 源URL | [http://119.78.100.186/handle/113462/133517]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhou, Guangming; Chen, Weiqiang |
| 作者单位 | 1.Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, New York, NY USA 2.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Gansu, Peoples R China 3.Soochow Univ, State Key Lab Radiat Med & Protect,Med Coll, Sch Radiat Med & Protect,Inst Space Life Sci, Collaborat Innovat Ctr Radiol Med,Jiangsu Higher, Suzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Nie, Jing,Hu, Wentao,Pei, Hailong,et al. Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2019,93(5):874-882. |
| APA | Nie, Jing.,Hu, Wentao.,Pei, Hailong.,Zhou, Guangming.,Chen, Weiqiang.,...&Zhang, Jian.(2019).Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.CHEMICAL BIOLOGY & DRUG DESIGN,93(5),874-882. |
| MLA | Nie, Jing,et al."Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate".CHEMICAL BIOLOGY & DRUG DESIGN 93.5(2019):874-882. |
入库方式： OAI收割
来源：近代物理研究所
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