title: Inhibiting delta-6 desaturase activity suppresses tumor growth in mice.
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.
authors.affiliation: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.forename: Xiying
authors.initials: X
authors.lastname: Qu
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wan
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Chun
authors.initials: C
authors.lastname: Cai
authors.forename: Keyuan
authors.initials: K
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Steven Y
authors.initials: SY
authors.lastname: Qian
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
mesh_terms: D000818:Animals; D015777:Eicosanoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D015316:Genetic Therapy; D050602:Linoleoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D015777:Eicosanoids; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D050602:Linoleoyl-CoA Desaturase