Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice
Qian, Steven Y.
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CitationHe, Chengwei, Xiying Qu, Jianbo Wan, Rong Rong, Lili Huang, Chun Cai, Keyuan Zhou, Yan Gu, Steven Y. Qian, and Jing X. Kang. 2012. Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS ONE 7(10): e47567.
AbstractRecent 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.
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