Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression

Abstract

Background Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare the effect of fish oil, olive oil, corn oil, and animal fat on PCa progression. Methods A total of 96 male SCID mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a fish oil, olive oil, corn oil, or animal fat-based Western diet (35% kcals from fat). Animals were euthanized when tumors reached 1,000mm3. Serum was collected at sacrifice and assayed for PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Tumors were also assayed for PGE-2 and COX-2 levels and global gene expression analyzed using Affymetrix microarrays. Results Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish oil consumption was associated with improved survival, relative to other dietary groups (p=0.014). On gene expression analyses, the fish oil group had decreased signal in pathways related to mitochondrial physiology and insulin synthesis/secretion. Conclusions In this xenograft model, we found that consuming a diet in which fish oil was the only fat source slowed tumor growth and improved survival, compared to mice consuming diets composed of olive oil, corn oil, or animal fat. While prior studies showed that the amount of fat is important for PCa growth, the current study suggests that type of dietary fat consumed may also be important.

The strategies to control prostate cancer by chemoprevention approaches

“…Among these are omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (Figure 1D). In a mouse xenograft model of PCA, mice fed only fish oil exhibited slower tumor growth and reduced mortality as compared to mice fed other fat sources [108]. This is consistent with a meta-analysis of case-control and cohort studies finding that incidence of PCA was not affected by consumption of fish, but mortality due to PCA was significantly reduced [109].…”

Effect of a Low-Fat Fish Oil Diet on Proinflammatory Eicosanoids and Cell-Cycle Progression Score in Men Undergoing Radical Prostatectomy

“…While a LFFO intervention resulted in lower prostate cancer proliferation (Ki-67) in our preprostatectomy Phase II trial (33), there was no effect on IGF-1 (primary outcome), COX-2 or PGE-2 levels suggesting that alternative mechanisms may be responsible for the observed anti-proliferative effects. Similarly, Lloyd et al recently published a xenograft study demonstrating that a fish oil based diet slowed prostate cancer progression but did not affect the IGF-1 axis or the COX2/PGE2 pathway compared to olive oil, corn oil or animal fat diets (6). These results led us to hypothesize that a LFFO diet may induce a reduction in serum levels of two major products of arachidonic acid metabolism, 15(S)-HETE and LTB4, through lipoxygenase pathways.…”

“…There is an ever-growing need to find new strategies to prevent the development of prostate cancer or to slow disease progression. Pre-clinical studies utilizing xenografts and genetically engineered mouse models demonstrated that reducing dietary fat from corn oil (omega-6 fatty acids) and increasing fish oil intake (omega-3 fatty acids) delays the development and progression of prostate cancer (3-6). Epidemiologic studies also found that a high-fat diet and low intake of omega-3 fatty acids were associated with increased risk of developing prostate cancer and increased risk of advanced disease (7-10).…”

TRAMP Prostate Tumor Growth Is Slowed by Walnut Diets Through Altered IGF-1 Levels, Energy Pathways, and Cholesterol Metabolism

“…[16][17][18][19] In animal studies, the Freedland's group showed using mouse PCa xenograft models that decreased saturated fat diets did not extend survival and that fish oil-fed mice outlived those fed corn oil, olive oil, or animal fat diets. 20,21 In our previous study, we found that WW, high-fat diets reduced TRAMP mouse prostate tumor size and growth compared to a soybean oil, high-fat diet. 8 Hardman and Ion found that the growth of implanted MDA-MB231 human breast cancer cells in female nude mice and later the growth of large T-antigen-driven mammary tumors in female transgenic mice were slowed by a walnut-enriched diet versus a corn oil-based diet fed either throughout (i.e., in utero and then after birth) or after weaning.…”

“…Recently, fish oil diet's PCa benefits have been related to changes in the mitochondrial activity and insulin synthesis/secretion. 21 Recent work has shown that a high-fat diet can drive prostate differentiation and this can be opposed by thiazolidinedione, a PPARc agonist. 37 In addition, the PPAR activity has been proposed to directly or indirectly modulate the supply of glucose and lipids for prostate metabolism.…”