Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis

doi:10.1007/s00253-018-9058-6

	Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis
	Xie, Wei 1,2; Zhang, Wei 3; Sun, Mingwei 1; Lu, Chunhua 1; Shen, Yuemao 1,4
刊名	APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
	2018-07-01
卷号	102 期号:14 页码:5965-5975
关键词	Deacetylmycoepoxydiene (DA-MED) GTPase Rac1 Autophagy Apoptosis Lung cancer p53-null human non-small cell lung cancer (NSCLC)
ISSN号	0175-7598
DOI	10.1007/s00253-018-9058-6
英文摘要	Lung cancer is the second most common cause of cancer-related death in the world. Most cases of lung cancer are not curable, especially non-small cell lung cancer (NSCLC). Thus, novel treatment targets for this malignant disease are urgently needed. Here, we demonstrate the feasibility of Rac1 in treating p53-null human NSCLC H1299 as a novel drug target. Deacetylmycoepoxydiene (DA-MED), a cytotoxic natural polyketide, functions as a Rac1 agonist in p53-null NSCLC H1299 cells. DA-MED treatment drives Rac1 activation and promotes robust production of reactive oxygen species, activating mitochondrial permeability transition and the intrinsic apoptotic pathway. Knockdown of Rac1 decreases ROS production in DA-MED-treated cells, resulting in a concomitant decrease in DA-MED-induced apoptosis. DA-MED-activated Rac1 induces autophagy by inhibiting mammalian target of rapamycin, leading to anti-apoptotic and anti-metastatic effects. Therefore, this study provides novel insight into the complex cytotoxic and pro-survival mechanisms associated with a potent Rac1 agonist and suggests that further development of more potent Rac1 agonists could be an effective strategy for future non-small cell lung cancer treatments.
资助项目	National Natural Science Foundation of China[91,313,303] ; National Natural Science Foundation of China[81,373,304] ; National Natural Science Foundation of China[U1405223] ; Program for Changjiang Scholars and Innovative Research Team in University[IRT_17R68] ; National Natural Science Funds for Distinguished Young Scholars[30325044] ; Postdoctoral innovation fund of Shandong Province[201502026]
WOS关键词	LUNG-CANCER ; MUTANT P53 ; CELLS ; ACTIVATION ; PHOSPHORYLATION ; MYCOEPOXYDIENE ; INVOLVEMENT ; INVASION ; RAS
WOS研究方向	Biotechnology & Applied Microbiology
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000435986500013
资助机构	National Natural Science Foundation of China ; Program for Changjiang Scholars and Innovative Research Team in University ; National Natural Science Funds for Distinguished Young Scholars ; Postdoctoral innovation fund of Shandong Province
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn/handle/337004/12480]
专题	中国科学院青岛生物能源与过程研究所
通讯作者	Shen, Yuemao
作者单位	1.Shandong Univ, Sch Pharmaceut Sci, Key Lab Chem Biol, Minist Educ, 44 West Wenhua Rd, Jinan 250120, Shandong, Peoples R China 2.Shandong Normal Univ, Key Lab Anim Resistance Biol Shandong Prov, Key Lab Mol & Nano Probes, Inst Biomed Sci,Coll Life Sci,Minist Educ, 88 East Wenhua Rd, Jinan 250014, Shandong, Peoples R China 3.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Key Lab Biofuels, Shandong Prov Key Lab Energy Genet, 189 Songling Rd, Qingdao 266101, Shandong, Peoples R China 4.Shandong Univ, State Key Lab Microbial Technol, Jinan 250100, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Xie, Wei,Zhang, Wei,Sun, Mingwei,et al. Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis[J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,2018,102(14):5965-5975.
APA	Xie, Wei,Zhang, Wei,Sun, Mingwei,Lu, Chunhua,&Shen, Yuemao.(2018).Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis.APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,102(14),5965-5975.
MLA	Xie, Wei,et al."Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis".APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 102.14(2018):5965-5975.