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Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice
He C.; Qu X.; Wan J.; Rong R.; Huang L.; Cai C.; Zhou K.; Gu Y.; Qian S.Y.; Kang J.X.
2012
Source PublicationPLoS ONE
ISSN19326203
Volume7Issue:10
Abstract

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n-6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n-6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n-6 AA and increased D6D activity can lead to enhanced n-6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention. © 2012 He et al.

DOI10.1371/journal.pone.0047567
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000310310200052
The Source to ArticleScopus
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Cited Times [WOS]:31   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorKang J.X.
Affiliation1.Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
2.Laboratory for Genetics, Nutrition and Health, Guangdong Medical College, Zhanjiang, Guangdong, P. R. China
3.Department of Pharmaceutical Science, North Dakota State University, Fargo, North Dakota, United States of America
4.State Key Laboratory of Quality Research in Chinese Medicine (UM), Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
Recommended Citation
GB/T 7714
He C.,Qu X.,Wan J.,et al. Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice[J]. PLoS ONE,2012,7(10).
APA He C..,Qu X..,Wan J..,Rong R..,Huang L..,...&Kang J.X..(2012).Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice.PLoS ONE,7(10).
MLA He C.,et al."Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice".PLoS ONE 7.10(2012).
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