Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer

doi:10.1016/j.canlet.2020.01.035

	Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer
	Xiao, Ruoxuan 1,2,3; Ding, Chunyong 1,3; Zhu, Hongwen 1,2; Liu, Xia 2; Gao, Jing 1,2; Liu, Qian 1,2,3; Lu, Dayun 1,2,3; Zhang, Naixia 2,3; Zhang, Ao 1,3; Zhou, Hu 1,2,3
刊名	CANCER LETTERS
	2020
卷号	475 页码:22-33
关键词	Artemisinin NSCLC ASNS ER stress
ISSN号	0304-3835
DOI	10.1016/j.canlet.2020.01.035
通讯作者	Zhang, Naixia(nxzhang@simm.ac.cn) ; Zhang, Ao(aozhang@simm.ac.cn) ; Zhou, Hu(zhouhu@simm.ac.cn)
英文摘要	Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality. Artemisinin (ART) and SOMCL-14.221 (221), a spirobicyclic analogue of ART, have been reported to inhibit the proliferation of A549 cells with unclear underlying mechanism. In the present study, we validated that both ART and 221 inhibited the proliferation and migration of NSCLC cells and the growth of A549 xenograft tumors without appreciable toxicity. The proteomic data revealed proteins upregulated in ART and 221 groups were involved in "response to endoplasmic reticulum stress" and "amino acid metabolism". Asparagine synthetase (ASNS) was identified as a key node protein in these processes. Interestingly, knockdown of ASNS improved the antitumor potency of ART and 221 in vitro and in vivo, and treatments with ART and 221 disordered the amino acid metabolism of A549 cells. Moreover, ART and 221 activated ER stress, and inhibition of ER stress abolished the anti-proliferative effects of ART and 221. In conclusion, this study demonstrates that ART and 221 suppress tumor growth by triggering ER stress, and the inhibition of ASNS enhances the antitumor activity of ART and 221, which provides new strategy for drug combination therapy.
资助项目	National Key Research and Development Program from the Ministry of Science and Technology of China[2017YFC1700200] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002] ; National Natural Science Foundation of China[31800693] ; National Natural Science Foundation of China[21877120] ; National Natural Science Foundation of China[81430080] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development of Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020320] ; Innovation Project of Instrument and Equipment Function Development of the Chinese Academy of Sciences
WOS关键词	UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; UP-REGULATION ; INDUCED APOPTOSIS ; DNA-DAMAGE ; IN-VITRO ; ARTEMISININ ; EXPRESSION ; GENE ; RECEPTOR
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000521111300004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280973]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Naixia; Zhang, Ao; Zhou, Hu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Xiao, Ruoxuan,Ding, Chunyong,Zhu, Hongwen,et al. Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer[J]. CANCER LETTERS,2020,475:22-33.
APA	Xiao, Ruoxuan.,Ding, Chunyong.,Zhu, Hongwen.,Liu, Xia.,Gao, Jing.,...&Zhou, Hu.(2020).Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer.CANCER LETTERS,475,22-33.
MLA	Xiao, Ruoxuan,et al."Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer".CANCER LETTERS 475(2020):22-33.