Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line

doi:10.1016/j.jchromb.2016.01.003

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 天然药物化学研究室

	Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line
	Gao, Dan 2,3,4; Wang, Yini 2,4; Xie, Weiyi 2,4; Yang, Ti 2,4; Jiang, Yuyang 1,3; Guo, Yuewei5 ; Guan, Jin 6; Liu, Hongxia 3,4
刊名	JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
	2016-03-01
卷号	1014 页码:17-23
关键词	Metabolomics UPLC/Q-TOF MS Flexibilide HCT-116 cells Action mechanism
ISSN号	1570-0232
DOI	10.1016/j.jchromb.2016.01.003
文献子类	Article
英文摘要	A marine natural compound flexibilide isolated from the soft coral Sinularia flexibilis has been found to have antitumor activity. However, its pharmacological mechanism on tumor cells has not been studied. Herein, an ultra-performance liquid chromatography coupled to quadrupole time of-flight mass spectrometry (UPLC/Q-TOF MS) based metabolomics approach was established to investigate the antitumor effect of flexibilide on HCT-116 cells and its action mechanism. Q-TOF MS and MS/MS were used to identify significantly different metabolites. Comparing flexibilide-treated HCT-116 cells group with control group (dimethyl sulfoxide), 19 distinct metabolites involved in sphingolipid metabolism, alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, glycerophospholipid metabolism, pyrimidine metabolism and others were discovered and identified. The significant decrease of phosphatidylcholine (PC) and phosphocholine levels and increase of lysophosphatidylcholine (LysoPC) levels in flexibilide treated cells suggested down-regulation of PC biosynthesis pathway. The decrease of sphingolipids reflected the lesions of cell membrane, and the up-regulation of sphingosine-1-phosphate indicated that TRAF2 and caspase-8 were likely to be activated by flexibilide and further caused cell apoptosis. Furthermore, TCA cycle was deemed to be down-regulated after flexibilide treatment, which might lead to an unsustainable of mitochondrial transmembrane potential MMP). The further measured descreased MMP with the increasing concentration of flexibilide treatment indiciated the dysfunction of mitochondrial which might finally lead to apoptosis. The UPLC/Q-TOF MS based metabolomics approach provides new insights into the mechanistic studies of flexibilide on tumor cells, which benefit its further improvement and application. (C) 2016 Published by Elsevier B.V.
资助项目	National High Technology Research and Development Program of China (863 Program)[2012AA020305] ; National High Technology Research and Development Program of China (863 Program)[2013AA092902] ; National Natural Science Foundation of China[21475073] ; National Youth Science Foundation[21305074] ; Natural Science Foundation of Guangdong Province[2014A030313757]
WOS关键词	SOFT CORAL ; SINULARIA-FLEXIBILIS ; ACTION MECHANISM ; PRODUCTS ; METABOANALYST ; APOPTOSIS ; GLUTAMINE ; PROTEIN ; SERVER ; TRAF2
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000371549900003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276127]
专题	天然药物化学研究室
通讯作者	Guan, Jin; Liu, Hongxia
作者单位	1.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China; 2.Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China; 3.Tsinghua Univ, Grad Sch Shenzhen, State Key Lab Breeding Base Shenzhen Key Lab Chem, Shenzhen 518055, Peoples R China; 4.Key Lab Metabol Shenzhen, Shenzhen 518055, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 6.Shenyang Chem Technol Univ, Sch Appl Chem, Shenyang 110142, Peoples R China
推荐引用方式 GB/T 7714	Gao, Dan,Wang, Yini,Xie, Weiyi,et al. Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2016,1014:17-23.
APA	Gao, Dan.,Wang, Yini.,Xie, Weiyi.,Yang, Ti.,Jiang, Yuyang.,...&Liu, Hongxia.(2016).Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1014,17-23.
MLA	Gao, Dan,et al."Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1014(2016):17-23.