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	Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate
	Guo, Ziyang1; Pei, Hailong1; Nie, Jing1; Hu, Wentao1; Zhang, Jian1; Ding, Jiahan1; Pan, Shuxian1; Li, Bingyan1; Hei, Tom K.2; Chen, Weiqiang3
刊名	CHEMICAL BIOLOGY & DRUG DESIGN
	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.
收录类别	SCI
WOS关键词	CANCER-CELLS ; AUTOPHAGY ; THERAPY ; RESISTANCE ; APOPTOSIS ; MODEL ; DRUG
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal
语种	英语
出版者	WILEY
WOS记录号	WOS:000468814500017
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2555445
专题	寒区旱区环境与工程研究所
通讯作者	Chen, Weiqiang; Zhou, Guangming
作者单位	1.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 2.Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, New York, NY USA 3.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Guo, Ziyang,Pei, Hailong,Nie, Jing,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	Guo, Ziyang.,Pei, Hailong.,Nie, Jing.,Hu, Wentao.,Zhang, Jian.,...&Zhou, Guangming.(2019).Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.CHEMICAL BIOLOGY & DRUG DESIGN,93(5),874-882.
MLA	Guo, Ziyang,et al."Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate".CHEMICAL BIOLOGY & DRUG DESIGN 93.5(2019):874-882.

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