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

severe combined immunodeficient mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a Western diet based on fish oil, olive oil, corn oil

or animal fat (35% kilocalories from fat). Animals were euthanized when tumor volumes reached 1000 mm3. Serum was collected at death and assayed for PSA, insulin, insulin-like growth

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 with that in mice consuming

diets composed of olive oil, corn oil or animal fat. Although prior studies showed that the _amount_ of fat is important for PCa growth, this study suggests that the _type_ of dietary fat

consumed may also be important. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

institution Subscribe to this journal Receive 4 print issues and online access $259.00 per year only $64.75 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access

to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our

FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE EFFECTS OF GLYCEMIC INDEX ON PROSTATE CANCER PROGRESSION IN A XENOGRAFT MOUSE MODEL Article Open access 11

December 2023 A STEARATE-RICH DIET AND OLEATE RESTRICTION DIRECTLY INHIBIT TUMOR GROWTH VIA THE UNFOLDED PROTEIN RESPONSE Article Open access 02 December 2024 WEIGHT LOSS AND METABOLIC

EFFECTS OF AN ALDH1A1-SPECIFIC INHIBITOR, FSI-TN42, IN A DIET INDUCED MOUSE MODEL OF OBESITY Article 11 November 2024 REFERENCES * Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ . Cancer

statistics, 2009. _CA Cancer J Clin_ 2009; 59: 225–249. Article  PubMed  Google Scholar  * Hsing AW, Tsao L, Devesa SS . International trends and patterns of prostate cancer incidence and

mortality. _Int J Cancer_ 2000; 85: 60–67. Article  CAS  PubMed  Google Scholar  * Kolonel LN, Nomura AM, Cooney RV . Dietary fat and prostate cancer: current status. _J Natl Cancer Inst_

1999; 91: 414–428. Article  CAS  PubMed  Google Scholar  * Villeneuve PJ, Johnson KC, Kreiger N, Mao Y . Risk factors for prostate cancer: results from the Canadian National Enhanced Cancer

Surveillance System. The Canadian Cancer Registries Epidemiology Research Group. _Cancer Causes Control_ 1999; 10: 355–367. Article  CAS  Google Scholar  * Kolonel LN . Fat, meat, and

prostate cancer. _Epidemiol Rev_ 2001; 23: 72–81. Article  CAS  PubMed  Google Scholar  * Chan JM, Gann PH, Giovannucci EL . Role of diet in prostate cancer development and progression. _J

Clin Oncol_ 2005; 23: 8152–8160. Article  CAS  PubMed  Google Scholar  * Clinton SK, Giovannucci E . Diet, nutrition, and prostate cancer. _Annu Rev Nutr_ 1998; 18: 413–440. Article  CAS 

PubMed  Google Scholar  * Crowe FL, Key TJ, Appleby PN, Travis RC, Overvad K, Jakobsen MU _et al_. Dietary fat intake and risk of prostate cancer in the European Prospective Investigation

into Cancer and Nutrition. _Am J Clin Nutr_ 2008; 87: 1405–1413. Article  CAS  PubMed  Google Scholar  * Norrish AE, Skeaff CM, Arribas GL, Sharpe SJ, Jackson RT . Prostate cancer risk and

consumption of fish oils: a dietary biomarker-based case–control study. _Br J Cancer_ 1999; 81: 1238–1242. Article  CAS  PubMed  PubMed Central  Google Scholar  * Terry P, Lichtenstein P,

Feychting M, Ahlbom A, Wolk A . Fatty fish consumption and risk of prostate cancer. _Lancet_ 2001; 357: 1764–1766. Article  CAS  PubMed  Google Scholar  * Augustsson K, Michaud DS, Rimm EB,

Leitzmann MF, Stampfer MJ, Willett WC _et al_. A prospective study of intake of fish and marine fatty acids and prostate cancer. _Cancer Epidemiol Biomarkers Prev_ 2003; 12: 64–67. CAS 

PubMed  Google Scholar  * de Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N . Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced

cancer rate. _Arch Intern Med_ 1998; 158: 1181–1187. Article  CAS  PubMed  Google Scholar  * Godley PA, Campbell MK, Gallagher P, Martinson FE, Mohler JL, Sandler RS . Biomarkers of

essential fatty acid consumption and risk of prostatic carcinoma. _Cancer Epidemiol Biomarkers Prev_ 1996; 5: 889–895. CAS  PubMed  Google Scholar  * Mills PK, Beeson WL, Phillips RL, Fraser

GE . Cohort study of diet, lifestyle, and prostate cancer in Adventist men. _Cancer_ 1989; 64: 598–604. Article  CAS  Google Scholar  * Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR, Heston WD

. Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. _J Natl Cancer Inst_ 1995; 87: 1456–1462. Article  CAS  PubMed  Google Scholar  * Ngo TH,

Barnard RJ, Anton T, Tran C, Elashoff D, Heber D _et al_. Effect of isocaloric low-fat diet on prostate cancer xenograft progression to androgen independence. _Cancer Res_ 2004; 64:

1252–1254. Article  CAS  PubMed  Google Scholar  * Ngo TH, Barnard RJ, Cohen P, Freedland S, Tran C, deGregorio F _et al_. Effect of isocaloric low-fat diet on human LAPC-4 prostate cancer

xenografts in severe combined immunodeficient mice and the insulin-like growth factor axis. _Clin Cancer Res_ 2003; 9: 2734–2743. CAS  PubMed  Google Scholar  * Kobayashi N, Barnard RJ,

Henning SM, Elashoff D, Reddy ST, Cohen P _et al_. Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin

E2. _Clin Cancer Res_ 2006; 12: 4662–4670. Article  CAS  PubMed  PubMed Central  Google Scholar  * Berquin IM, Min Y, Wu R, Wu J, Perry D, Cline JM _et al_. Modulation of prostate cancer

genetic risk by omega-3 and omega-6 fatty acids. _J Clin Invest_ 2007; 117: 1866–1875. Article  CAS  PubMed  PubMed Central  Google Scholar  * Freedland SJ, Mavropoulos J, Wang A, Darshan M,

Demark-Wahnefried W, Aronson WJ _et al_. Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. _Prostate_ 2008; 68: 11–19. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Lloyd JC, Antonelli JA, Phillips TE, Masko EM, Thomas JA, Poulton SH _et al_. Effect of isocaloric low fat diet on prostate cancer xenograft progression in a

hormone deprivation model. _J Urol_ 2010; 183: 1619–1624. Article  CAS  PubMed  PubMed Central  Google Scholar  * Klein KA, Reiter RE, Redula J, Moradi H, Zhu XL, Brothman AR _et al_.

Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. _Nat Med_ 1997; 3: 402–408. Article  CAS  PubMed  Google Scholar  * Gravina GL,

Marampon F, Giusti I, Carosa E, Di Sante S, Ricevuto E _et al_. Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models. _Int J

Oncol_ 2012; 40: 711–720. CAS  PubMed  Google Scholar  * Emonds KM, Swinnen JV, Lerut E, Koole M, Mortelmans L, Mottaghy FM . Evaluation of androgen-induced effects on the uptake of

[18F]FDG, [11C]choline and [11C]acetate in an androgen-sensitive and androgen-independent prostate cancer xenograft model. _EJNMMI Res_ 2013; 3: 31. Article  PubMed  PubMed Central  Google

Scholar  * Thomas R, Sharifi N . SOD mimetics: a novel class of androgen receptor inhibitors that suppresses castration-resistant growth of prostate cancer. _Mol Cancer Ther_ 2012; 11:

87–97. Article  CAS  PubMed  Google Scholar  * Mukherjee P, Sotnikov AV, Mangian HJ, Zhou JR, Visek WJ, Clinton SK . Energy intake and prostate tumor growth, angiogenesis, and vascular

endothelial growth factor expression. _J Natl Cancer Inst_ 1999; 91: 512–523. Article  CAS  PubMed  Google Scholar  * Thomas JA 2nd, Antonelli JA, Lloyd JC, Masko EM, Poulton SH, Phillips TE

_et al_. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. _Prostate Cancer Prostatic Dis_ 2010; 13: 350–355. Article  CAS  PubMed  Google Scholar  * Chen JL,

Merl D, Peterson CW, Wu J, Liu PY, Yin H _et al_. Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. _PLoS Genet_ 2010; 6: 1–18. CAS  Google

Scholar  * Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA _et al_. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression

profiles. _Proc Natl Acad Sci USA_ 2005; 102: 15545–15550. Article  CAS  PubMed  Google Scholar  * Kolonel LN . Nutrition and prostate cancer. _Cancer Causes Control_ 1996; 7: 83–94. Article

  CAS  PubMed  Google Scholar  * Lee MM, Wang RT, Hsing AW, Gu FL, Wang T, Spitz M . Case–control study of diet and prostate cancer in China. _Cancer Causes Control_ 1998; 9: 545–552.

Article  CAS  PubMed  Google Scholar  * Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR _et al_. Prostate cancer in relation to diet, physical activity, and body size in

blacks, whites, and Asians in the United States and Canada. _J Natl Cancer Inst_ 1995; 87: 652–661. Article  CAS  PubMed  Google Scholar  * Park SY, Murphy SP, Wilkens LR, Henderson BE,

Kolonel LN . Fat and meat intake and prostate cancer risk: the multiethnic cohort study. _Int J Cancer_ 2007; 121: 1339–1345. Article  CAS  PubMed  Google Scholar  * Ramon JM, Bou R, Romea

S, Alkiza ME, Jacas M, Ribes J _et al_. Dietary fat intake and prostate cancer risk: a case–control study in Spain. _Cancer Causes Control_ 2000; 11: 679–685. Article  CAS  PubMed  Google

Scholar  * Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D . Cancer and Mediterranean dietary traditions. _Cancer Epidemiol Biomarkers Prev_ 2000; 9: 869–873. CAS  PubMed  Google Scholar 

* Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM _et al_. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical

prostatectomy. _Cancer Prev Res (Phila)_ 2011; 4: 2062–2071. Article  CAS  Google Scholar  * Li Z, Aronson WJ, Arteaga JR, Hong K, Thames G, Henning SM _et al_. Feasibility of a

low-fat/high-fiber diet intervention with soy supplementation in prostate cancer patients after prostatectomy. _Eur J Clin Nutr_ 2008; 62: 526–536. Article  CAS  PubMed  Google Scholar  *

Connolly JM, Coleman M, Rose DP . Effects of dietary fatty acids on DU145 human prostate cancer cell growth in athymic nude mice. _Nutr Cancer_ 1997; 29: 114–119. Article  CAS  PubMed 

Google Scholar  * Hardman WE . (n-3) fatty acids and cancer therapy. _J Nutr_ 2004; 134 (Suppl 12): 3427S–3430S. Article  CAS  PubMed  Google Scholar  * Needleman P, Raz A, Minkes MS,

Ferrendelli JA, Sprecher H . Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. _Proc Natl Acad Sci USA_ 1979; 76: 944–948. Article  CAS 

PubMed  Google Scholar  * McKeehan WL, Adams PS, Rosser MP . Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and

possibly prolactin, but not androgen, on normal rat prostate epithelial cells in serum-free, primary cell culture. _Cancer Res_ 1984; 44: 1998–2010. CAS  PubMed  Google Scholar  * Hsing AW,

Chua S Jr, Gao YT, Gentzschein E, Chang L, Deng J _et al_. Prostate cancer risk and serum levels of insulin and leptin: a population-based study. _J Natl Cancer Inst_ 2001; 93: 783–789.

Article  CAS  PubMed  Google Scholar  * Lubik AA, Gunter JH, Hendy SC, Locke JA, Adomat HH, Thompson V _et al_. Insulin increases _de novo_ steroidogenesis in prostate cancer cells. _Cancer

Res_ 2011; 71: 5754–5764. Article  CAS  PubMed  Google Scholar  * Armstrong P, Kelley DS, Newman JW, Staggers FE Sr, Hartiala J, Allayee H _et al_. Arachidonate 5-lipoxygenase gene variants

affect response to fish oil supplementation by healthy African Americans. _J Nutr_ 2012; 142: 1417–1428. Article  CAS  PubMed  PubMed Central  Google Scholar  * Calle EE, Rodriguez C,

Walker-Thurmond K, Thun MJ . Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. _N Engl J Med_ 2003; 348: 1625–1638. Article  Google Scholar  *

Whitley BM, Moreira DM, Thomas JA, Aronson WJ, Terris MK, Presti JC Jr _et al_. Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the

Shared Equal Access Regional Cancer Hospital database. _Prostate Cancer Prostatic Dis_ 2011; 14: 361–366. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We would

like to acknowledge the contributions of Jodi Antonelli, Jean-Alfred Thomas II and Tameika E Phillips. This study was supported by the Department of Veterans Affairs; Division of Urology,

Department of Surgery, Duke University; Prostate Cancer Foundation; NIH Training Grant 1 TL1 RR024126; and NIH 5R01 CA131235-03. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of

Surgery, Durham VA Medical Center, Durham, NC, USA J C Lloyd, E M Masko, C Wu & S J Freedland * Division of Urology, Department of Surgery, Duke Prostate Center, Duke University School

of Medicine, Durham, NC, USA J C Lloyd, E M Masko, C Wu & S J Freedland * Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA M M

Keenan, D M Pilla & J-TA Chi * Department of Urology, University of California—Los Angeles, Los Angeles,, CA, USA W J Aronson * Department of Pathology, Duke University School of

Medicine, Durham, NC, USA S J Freedland Authors * J C Lloyd View author publications You can also search for this author inPubMed Google Scholar * E M Masko View author publications You can

also search for this author inPubMed Google Scholar * C Wu View author publications You can also search for this author inPubMed Google Scholar * M M Keenan View author publications You can

also search for this author inPubMed Google Scholar * D M Pilla View author publications You can also search for this author inPubMed Google Scholar * W J Aronson View author publications

You can also search for this author inPubMed Google Scholar * J-TA Chi View author publications You can also search for this author inPubMed Google Scholar * S J Freedland View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to S J Freedland. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no

conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website . SUPPLEMENTARY INFORMATION SUPPLEMENTARY

FIGURE 1 (JPG 68 KB) SUPPLEMENTARY FIGURE LEGEND (DOC 33 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lloyd, J., Masko, E., Wu, C. _et al._ Fish

oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression. _Prostate Cancer Prostatic Dis_

16, 285–291 (2013). https://doi.org/10.1038/pcan.2013.19 Download citation * Received: 13 March 2013 * Revised: 17 June 2013 * Accepted: 19 June 2013 * Published: 23 July 2013 * Issue Date:

December 2013 * DOI: https://doi.org/10.1038/pcan.2013.19 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable

link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * prostatic neoplasms * diet * fat