Abstract
For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceautical target for the treatment of cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1520-1526 |
| Number of pages | 7 |
| Journal | Carcinogenesis |
| Volume | 26 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
Cite this
Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells. / Hughes-Fulford, Millie; Tjandrawinata, Raymond R.; Li, Chai-Fei; Sayyah, Sina.
In: Carcinogenesis, Vol. 26, No. 9, 01.09.2005, p. 1520-1526.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells
AU - Hughes-Fulford, Millie
AU - Tjandrawinata, Raymond R.
AU - Li, Chai-Fei
AU - Sayyah, Sina
PY - 2005/9/1
Y1 - 2005/9/1
N2 - For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceautical target for the treatment of cancer.
AB - For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceautical target for the treatment of cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=24144488379&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgi112
DO - 10.1093/carcin/bgi112
M3 - Article
C2 - 15878913
AN - SCOPUS:24144488379
VL - 26
SP - 1520
EP - 1526
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 9
ER -