Prostate Tumor Growth and Recurrence Can Be Modulated by O6:O3 Ratio

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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.

Kelavkar UP, Hutzley J, Dhir R, Kim P, KG, McHugh K.

Department of Urology and Cancer Institute, University of Pittsburgh,

Pittsburgh, PA, USA, Email: kelavkarup@....

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.

PMID: 16611404 [PubMed - in process]