QIBEBT-IR
Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis
Xie, Wei1,2; Zhang, Wei3; Sun, Mingwei1; Lu, Chunhua1; Shen, Yuemao1,4
2018-07-01
Source PublicationAPPLIED MICROBIOLOGY AND BIOTECHNOLOGY
ISSN0175-7598
Volume102Issue:14Pages:5965-5975
AbstractLung 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.
KeywordDeacetylmycoepoxydiene (DA-MED) GTPase Rac1 Autophagy Apoptosis Lung cancer p53-null human non-small cell lung cancer (NSCLC)
DOI10.1007/s00253-018-9058-6
WOS KeywordLUNG-CANCER ; MUTANT P53 ; CELLS ; ACTIVATION ; PHOSPHORYLATION ; MYCOEPOXYDIENE ; INVOLVEMENT ; INVASION ; RAS
Language英语
Funding ProjectNational 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 Research AreaBiotechnology & Applied Microbiology
Funding OrganizationNational 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
WOS SubjectBiotechnology & Applied Microbiology
WOS IDWOS:000435986500013
PublisherSPRINGER
Citation statistics
Document Type期刊论文
Identifierhttp://ir.qibebt.ac.cn/handle/337004/12481
Collection中国科学院青岛生物能源与过程研究所
Corresponding AuthorShen, Yuemao
Affiliation1.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
Recommended Citation
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.
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