Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor
	Zou, ZZ; Hu, XY; Luo, T; Ming, ZN; Chen, XD; Xia, L; Luo, WS; Li, JJ; Xu, N; Chen, L; Cao, DS; Wen, M; Kong, FR; Peng, KJ; Xie, YZ; Li, X; Ma, DY; Yang, CY; Chen, CS; Yi, WJ; Liu, OS; Liu, SY; Luo, JL; Luo, ZY
	2021
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	12 期号:1
摘要	Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13693
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Zou, ZZ,Hu, XY,Luo, T,et al. Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Zou, ZZ.,Hu, XY.,Luo, T.,Ming, ZN.,Chen, XD.,...&Luo, ZY.(2021).Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.NATURE COMMUNICATIONS,12(1).
MLA	Zou, ZZ,et al."Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor".NATURE COMMUNICATIONS 12.1(2021).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023032946.pdf（4387KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文