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Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy.

Abstract
Evidence indicates that a diet rich in omega (omega)-6 polyunsaturated fatty acids (PUFAs) [e.g., linoleic acid (LA)] increases prostate cancer (PCa) risk, whereas a diet rich in omega-3 decreases risk. Precisely how these PUFAs affect disease development remains unclear. So we examined the roles that PUFAs play in PCa, and we determined if increased omega-3 consumption can impede tumor growth. We previously demonstrated an increased expression of an omega-6 LA-metabolizing enzyme, 15-lipoxygenase-1 (15-LO-1, ALOX15), in prostate tumor tissue compared with normal adjacent prostate tissue, and that elevated 15-LO-1 activity in PCa cells has a protumorigenic effect. A PCa cell line, Los Angeles Prostate Cancer-4 (LAPC-4), expresses prostate-specific antigen (PSA) as well an active 15-LO-1 enzyme. Therefore, to study whether or not the protumorigenic role of 15-LO-1 and dietary omega-6 LA can be modulated by altering omega-3 levels through diet, we surgically removed tumors caused by LAPC-4 cells (mouse model to simulate radical prostatectomy). Mice were then randomly divided into three different diet groups-namely, high omega-6 LA, high omega-3 stearidonic acid (SDA), and no fat-and examined the effects of omega-6 and omega-3 fatty acids in diet on LAPC-4 tumor recurrence by monitoring for PSA. Mice in these diet groups were monitored for food consumption, body weight, and serum PSA indicative of the presence of LAPC-4 cells. Fatty acid methyl esters from erythrocyte membranes were examined for omega-6 and omega-3 levels to reflect long-term dietary intake. Our results provide evidence that prostate tumors can be modulated by the manipulation of omega-6:omega-3 ratios through diet and that the omega-3 fatty acid SDA [precursor of eicosapentaenoic acid (EPA)] promotes apoptosis and decreases proliferation in cancer cells, causing decreased PSA doubling time, compared to omega-6 LA fatty acid, likely by competing with the enzymes of LA and AA pathways, namely, 15-LO-1 and cyclooxygenases (COXs). Thus, EPA and DHA (major components of fish oil) could potentially be promising dietary intervention agents in PCa prevention aimed at 15-LO-1 and COX-2 as molecular targets. These observations also provide clues as to its mechanisms of action.
AuthorsUddhav P Kelavkar, Justin Hutzley, Rajiv Dhir, Paul Kim, Kenneth G D Allen, Kevin McHugh
JournalNeoplasia (New York, N.Y.) (Neoplasia) Vol. 8 Issue 2 Pg. 112-24 (Feb 2006) ISSN: 1476-5586 [Electronic] Canada
PMID16611404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
Topics
  • Animals
  • Diet
  • Disease Models, Animal
  • Fatty Acids, Omega-3 (administration & dosage)
  • Fatty Acids, Omega-6 (administration & dosage)
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatectomy
  • Prostatic Neoplasms (pathology, surgery)
  • Recurrence
  • Transplantation, Heterologous

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