Inhibiting delta-6 desaturase activity suppresses tumor growth in mice.
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 bee...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3480421?pdf=render |
| _version_ | 1818020851782516736 |
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| author | Chengwei He Xiying Qu Jianbo Wan Rong Rong Lili Huang Chun Cai Keyuan Zhou Yan Gu Steven Y Qian Jing X Kang |
| author_facet | Chengwei He Xiying Qu Jianbo Wan Rong Rong Lili Huang Chun Cai Keyuan Zhou Yan Gu Steven Y Qian Jing X Kang |
| author_sort | Chengwei He |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T08:10:59Z |
| format | Article |
| id | doaj.art-61980e44f977430db3078b1e905cc24c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T08:10:59Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-61980e44f977430db3078b1e905cc24c2022-12-22T02:04:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4756710.1371/journal.pone.0047567Inhibiting delta-6 desaturase activity suppresses tumor growth in mice.Chengwei HeXiying QuJianbo WanRong RongLili HuangChun CaiKeyuan ZhouYan GuSteven Y QianJing X KangRecent 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.http://europepmc.org/articles/PMC3480421?pdf=render |
| spellingShingle | Chengwei He Xiying Qu Jianbo Wan Rong Rong Lili Huang Chun Cai Keyuan Zhou Yan Gu Steven Y Qian Jing X Kang Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS ONE |
| title | Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. |
| title_full | Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. |
| title_fullStr | Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. |
| title_full_unstemmed | Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. |
| title_short | Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. |
| title_sort | inhibiting delta 6 desaturase activity suppresses tumor growth in mice |
| url | http://europepmc.org/articles/PMC3480421?pdf=render |
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