133 articles - 10.09.10
1: Nutr Cancer. 2010 Apr;62(3):284-96.
Shaikh IA, Brown I, Wahle KW, Heys SD.
Cancer Medicine Group, Division of Applied Medicine, Medical School, University of Aberdeen, Aberdeen, UK.
The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20358465&dopt=ExternalLink
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PMID: 20358465 [PubMed - indexed for MEDLINE]2: Am J Clin Nutr. 2010 May;91(5):1185-94. Epub 2010 Mar 24.
Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, Clinton SK.
Department of Surgery, The Ohio State University, Columbus, OH, USA. lisa.yee@osumc.edu
BACKGROUND: Preclinical evidence of the preventive benefits of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/omega-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined. OBJECTIVE: To determine the dose effects of omega-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of omega-3 PUFAs in women at high risk of breast cancer. DESIGN: In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an omega-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo. RESULTS: All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with > or = 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 +/- 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported. CONCLUSIONS: Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of omega-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.
Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20335550&dopt=ExternalLink
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PMID: 20335550 [PubMed - indexed for MEDLINE]3: Bioorg Med Chem. 2010 Mar 1;18(5):1866-74. Epub 2010 Jan 25.
Harvey KA, Xu Z, Whitley P, Davisson VJ, Siddiqui RA.
Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Inc., 1800 N. Capital Ave., Indianapolis, IN 46202, USA.
The present study describes the characterization and evaluation of novel anticancer conjugates, 2,6-diisopropylphenol-docosahexaenoate (PP-DHA), and its analogues including 2,4-diisopropylphenol-docosahexaenoate (DIPP-DHA), 2-isopropylphenol-docosahexaenoate (IPP-DHA), 2-cyclohexanephenol-docosahexaenoate (CHP-DHA) and phenol-docosahexaenoate (P-DHA) on breast cancer cell lines. Representative breast cancer cell lines, based on estrogen alpha receptor (ER) and oncogene Her-2 expression, were used and include MDA-MB-231 (ER-negative, Her-2-negative), MCF-7 (ER-positive, Her-2-negative) AU565 (ER-negative, Her-2-positive) and MDA-MB-361 (ER-positive, Her-2-positive). The PP-DHA conjugate significantly inhibited cell growth and induced cell loss in the breast cancer cell lines similarly; however, this conjugate was not effective against normal mammary epithelial cells. The effect of various conjugates were in PP-DHA>IPP-DHA>DIPP-DHA>CHP-DHA>>P-DHA order. PP-DHA and IPP-DHA conjugates were stable in human and mouse serum. Furthermore, the non-hydrolyzable amide-linked conjugate analogues affected breast cancer cells in a manner similar to that of the ester-linked conjugates. This suggests that ester-linked PP-DHA and IPP-DHA conjugates were stable during treatment to breast cancer cells due to structural hindrance. PP-DHA did not affect PPARalpha or PPARgamma activities but its anticancer effects appear to be mediated in part though the inhibition of histone deacetylase (HDAC) activity. Further experiments are needed to confirm their molecular target and to test the effectiveness of these compounds in an in vivo model for their anticancer properties. In conclusion, these results suggest that the novel PP-DHA and IPP-DHA conjugates and their amide derivatives may be useful for the treatment of breast cancer. Copyright 2010 Elsevier Ltd. All rights reserved.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20153203&dopt=ExternalLink
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PMID: 20153203 [PubMed - indexed for MEDLINE]4: Carcinogenesis. 2010 Mar;31(3):489-95. Epub 2009 Dec 7.
Dimri M, Bommi PV, Sahasrabuddhe AA, Khandekar JD, Dimri GP.
Department of Medicine, NorthShore University HealthSystem Research Institute, 1001 University Place, Evanston, IL 60201, USA.
The polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), is overexpressed in several human malignancies including breast cancer. Aberrant expression of EZH2 has been associated with metastasis and poor prognosis in cancer patients. Despite the clear role of EZH2 in oncogenesis and therapy failure, not much is known about chemotherapeutics and chemopreventive agents that can suppress its expression and activity. Here, we show that dietary omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) can regulate the expression of EZH2 in breast cancer cells. The treatment of breast cancer cells with omega-3 PUFAs, but not omega-6 PUFAs, led to downregulation of EZH2. Studies using proteosome inhibitor MG132 suggested that omega-3 PUFAs induce degradation of the PcG protein EZH2 through posttranslational mechanisms. Furthermore, downregulation of EZH2 by omega-3 PUFAs was accompanied by a decrease in histone 3 lysine 27 trimethylation (H3K27me3) activity of EZH2 and upregulation of E-cadherin and insulin-like growth factor binding protein 3, which are known targets of EZH2. Treatment with omega-3 PUFAs also led to decrease in invasion of breast cancer cells, an oncogenic phenotype that is known to be associated with EZH2. Thus, our studies suggest that the PcG protein EZH2 is an important target of omega-3 PUFAs and that downregulation of EZH2 may be involved in the mediation of anti-oncogenic and chemopreventive effects of omega-3 PUFAs.
Publication Types: Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19969553&dopt=ExternalLink
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PMID: 19969553 [PubMed - indexed for MEDLINE]5: Br J Cancer. 2009 Dec 15;101(12):1978-85. Epub 2009 Nov 17.
Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O.
INSERM U921 Nutrition, Croissance et Cancer, Tours, France. bougnoux@med.univ-tours.fr
BACKGROUND: Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin. METHODS: This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n = 25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS). RESULTS: The objective response rate was 44%. With a mean follow-up time of 31 months (range 2-96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n = 12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%). CONCLUSION: DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.
Publication Types: Clinical Trial, Phase II Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19920822&dopt=ExternalLink
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PMID: 19920822 [PubMed - indexed for MEDLINE]6: Prog Lipid Res. 2010 Jan;49(1):76-86. Epub 2009 Aug 26.
Bougnoux P, Hajjaji N, Maheo K, Couet C, Chevalier S.
Inserm U921 Nutrition, Growth and Cancer, Universite Francois Rabelais de Tours, Tours, France. philippe.bougnoux@univ-tours.fr
Lifestyle and nutritional factors have been recognized to influence breast cancer survival, irrespective of genomic alterations that are the hallmarks of the disease. The biological and molecular mechanisms involved in the effects of dietary polyunsaturated fatty acids and breast cancer response to treatments in clinical and preclinical studies have been reviewed. Among nutrients, rumenic acid, a naturally occurring CLA isomer and n-3 docosahexaenoic acid (DHA) a highly unsaturated fatty acid, have emerged due to their potential to increase cancer treatment efficacy without additional side effects. In this review, we analyze the literature evidence that breast cancer treatment and outcome could be improved through an adjuvant dietary supplementation. Such an original approach would involve two successive phases of breast cancer treatment: an initial sensitization of residual tumor cells to chemotherapy and to radiation therapy with dietary DHA; then a prevention of metastatic re-growth with a prolonged rumenic acid supplementation. Safety is not anticipated to be a critical issue, although it has to be assessed in the long term. Dietary supplements, used in combination to anti-cancer agents, should be provided under medical prescription. Such an original use of fatty acids in breast cancer treatment could provide the lipid field with a new avenue to impact public health.
Publication Types: Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19715726&dopt=ExternalLink
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PMID: 19715726 [PubMed - indexed for MEDLINE]7: Cancer Causes Control. 2009 Nov;20(9):1715-21. Epub 2009 Aug 27.
Witt PM, Christensen JH, Schmidt EB, Dethlefsen C, Tjonneland A, Overvad K, Ewertz M.
Department of Oncology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 18-22, 9100, Aalborg, Denmark. p.witt@rn.dk
OBJECTIVE: The aim of this study was to investigate the association between the content of marine n-3 polyunsaturated fatty acids (PUFA) in adipose tissue, a biomarker for the long-term intake of seafood, and the subsequent development of breast cancer (BC). DESIGN: We designed a case-cohort study based on a cohort of healthy Danish women, who in the 1990 s donated adipose tissue biopsies to a biobank in order to investigate the role of diet for the development of cancer and chronic disease. During follow-up, incident cases of BC were identified through national registries, and the content of n-3 PUFA in adipose tissue was compared between cases and the cohort sample. RESULTS: During follow-up, 463 new cases of BC were identified. After adjusting for potential confounders, no significant association between the content of marine n-3 PUFA and BC was found. When comparing the highest with the lowest quintile, the hazard ratio (HR) was 0.96 (95% CI 0.64-1.43) for total marine n-3 PUFA, 0.84 (95% CI 0.58-1.23) for eicosapentaenoic acid (EPA), and 1.08 (95% CI 0.73-1.58) for docosahexaenoic acid (DHA). CONCLUSION: This study does not indicate any association between the content of total or individual marine n-3 PUFA in adipose tissue and development of BC.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19711189&dopt=ExternalLink
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PMID: 19711189 [PubMed - indexed for MEDLINE]8: Mol Cancer Res. 2009 Jul;7(7):1013-20. Epub 2009 Jun 30.
Altenburg JD, Siddiqui RA.
Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Indianapolis, IN 46202, USA.
Metastasis is the leading cause of death from breast cancer. A major factor of metastasis is the migration of cancerous cells to other tissues by way of up-regulated chemokine receptors, such as CXCR4, on the cell surface. Much is known of the beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on cancer; however, the mechanisms behind these effects are unclear. For this study, we investigated the effects of two n-3 PUFAs, docosahexaenoic acid and eicosapentaenoic acid, on CXCR4 expression and activity in the MDA-MB-231 breast cancer cell line. We compared the n-3 PUFAs with the saturated fatty acid stearic acid as a control. Treatment of the cells with n-3 PUFAs resulted in reduced surface expression of CXCR4, but had no effect on overall CXCR4 expression. Consequently, we found that the fatty acid treatment significantly reduced CXCR4-mediated cell migration. Successful CXCR4-mediated signaling and migration requires the cholesterol-rich membrane microdomains known as lipid rafts. Treatment with n-3 PUFAs disrupted the lipid raft domains in a manner similar to methyl-beta-cyclodextrin and resulted in a partial displacement of CXCR4, suggesting a possible mechanism behind the reduced CXCR4 activity. These results were not observed in cells treated with stearic acid. Together, our data suggest that n-3 PUFAs may have a preventative effect on breast cancer metastasis in vitro. This suggests a previously unreported potential benefit of n-3 PUFAs to patients with metastatic breast cancer. The data presented in this study may also translate to other disorders that involve up-regulated chemokine receptors.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19567784&dopt=ExternalLink
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PMID: 19567784 [PubMed - indexed for MEDLINE]9: BMC Cancer. 2009 Jun 30;9:216.
Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES.
Cancer Epidemiology Branch, Division of Cancer Epidemiology and Management, Research Institute, National Cancer Center, Gyeonggi, South Korea. jskim@ncc.re.kr
BACKGROUND: Although it is believed that fish omega-3 fatty acids may decrease breast cancer risk, epidemiological evidence has been inconclusive. This study examined the association between fish and fish omega-3 fatty acids intake with the risk of breast cancer in a case-control study of Korean women. METHODS: We recruited 358 incident breast cancer patients and 360 controls with no history of malignant neoplasm from the National Cancer Center Hospital between July 2007 and April 2008. The study participants were given a 103-item food intake frequency questionnaire to determine their dietary consumption of fish (fatty and lean fish) and omega-3 fatty acids derived from fish (eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)). RESULTS: Using a multivariate logistic regression model, high intake of fatty fish was associated with a reduced risk for breast cancer in both pre- and postmenopausal women (OR [95% CI] for highest vs. lowest intake quartiles, p for trend: 0.19 [0.08 to 0.45], p < 0.001 for premenopausal women, 0.27 [0.11 to 0.66], p = 0.005 for postmenopausal women). Similarly, reductions in breast cancer risk were observed among postmenopausal subjects who consumed more than 0.101 g of EPA (OR [95% CI]: 0.38 [0.15 to 0.96]) and 0.213 g of DHA (OR [95% CI]: 0.32 [0.13 to 0.82]) from fish per day compared to the reference group who consumed less than 0.014 g of EPA and 0.037 g of DHA per day. Among premenopausal women, there was a significant reduction in breast cancer risk for the highest intake quartiles of omega-3 fatty acids (ORs [95% CI]: 0.46 [0.22 to 0.96]), compared to the reference group who consumed the lowest quartile of intake. CONCLUSION: These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19566923&dopt=ExternalLink
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PMID: 19566923 [PubMed - indexed for MEDLINE]10: Acta Paediatr. 2009 Sep;98(9):1461-7. Epub 2009 Jun 1.
Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Bottcher MF, Falth-Magnusson K, Duchen K.
Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden. catrin.furuhjelm@lio.se
Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. Aim: To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. Methods: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. Results: The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). Conclusion: Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19489765&dopt=ExternalLink
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PMID: 19489765 [PubMed - indexed for MEDLINE]11: Br J Haematol. 2009 Apr;145(1):84-6. Epub 2009 Feb 4.
Musolino A, Panebianco M, Zendri E, Santini M, Di Nuzzo S, Ardizzoni A.
Medical Oncology Unit, University Hospital of Parma, Parma, Italy. antoninomusolino@hotmail.com
Bexarotene is approved for the treatment of cutaneous T cell lymphomas in patients refractory to at least one prior systemic therapy. Associated hypertriglyceridaemia requires monitoring, but can readily be managed with concomitant medication, such as fenofibrate. Here we report three cases of hypertriglyceridaemia secondary to bexarotene assumption, which was adequately managed with omega-3 fatty acids. If fenofibate-related side effects occur, or a statin is required to control low-density lipoprotein-cholesterol, omega-3 fatty acids should be considered as a good alternative therapy to lower lipid levels during bexarotene treatment.
Publication Types: Case Reports
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19208096&dopt=ExternalLink
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PMID: 19208096 [PubMed - indexed for MEDLINE]12: Asia Pac J Clin Nutr. 2008;17(4):612-9.
Miyake Y, Sasaki S, Tanaka K, Ohya Y, Matsunaga I, Yoshida T, Hirota Y, Oda H.
Department of Public Health, Fukuoka University, Fukuoka, Japan. miyake-y@fukuoka-u.ac.jp
Dietary factors may be important in the development of atopic eczema. It remains controversial whether n-3 polyunsaturated fatty acid intake is preventive against allergic disorders and whether n-6 polyunsaturated fatty acid intake increases the risk of allergic disorders. The current cross-sectional study examined the association between intake of fatty acids and foods high in fatty acids and the prevalence of atopic eczema. Study subjects were 1002 pregnant Japanese females. Current atopic eczema and atopic eczema after age 18 were defined as present if subjects had been treated with medications at some time in the previous 12 months and after reaching the age of 18, respectively. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Docosahexaenoic acid intake was statistically significantly related to a decreased prevalence of atopic eczema after age 18 and current atopic eczema. Inverse dose-response relationships with regard to consumption of n-3 polyunsaturated fatty acids, eicosapentaenoic acid, and fish and the ratio of n-3 to n-6 polyunsaturated fatty acids with atopic eczema were not observed although these dietary variables in the second tertile were inversely significantly associated with atopic eczema after age 18. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids, cholesterol, meat, eggs, or dairy products was not related to either of the outcomes for atopic eczema. Docosahexaenoic acid intake may be associated with a reduced prevalence of atopic eczema in pregnant Japanese females.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19114399&dopt=ExternalLink
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PMID: 19114399 [PubMed - indexed for MEDLINE]13: Am J Clin Nutr. 2009 Jan;89(1):265-76. Epub 2008 Dec 3.
Shannon J, King IB, Lampe JW, Gao DL, Ray RM, Lin MG, Stalsberg H, Thomas DB.
Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, USA. shannoja@ohsu.edu
BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.
Publication Types: Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19056601&dopt=ExternalLink
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PMID: 19056601 [PubMed - indexed for MEDLINE]14: Int J Cancer. 2009 Feb 15;124(4):924-31.
Thiebaut AC, Chajes V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Benichou J, Clavel-Chapelon F.
INSERM, ERI-20, Institut Gustave Roussy, Villejuif Cedex, France.
Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19035453&dopt=ExternalLink
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PMID: 19035453 [PubMed - indexed for MEDLINE]15: Breast Cancer Res Treat. 2009 Nov;118(1):213-28. Epub 2008 Oct 26.
Ghosh-Choudhury T, Mandal CC, Woodruff K, St Clair P, Fernandes G, Choudhury GG, Ghosh-Choudhury N.
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
The molecular mechanism for the beneficial effect of fish oil on breast tumor growth is largely undefined. Using the xenograft model in nude mice, we for the first time report that the fish oil diet significantly increased the level of PTEN protein in the breast tumors. In addition, the fish oil diet attenuated the PI 3 kinase and Akt kinase activity in the tumors leading to significant inhibition of NFkappaB activation. Fish oil diet also prevented the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in the breast tumors with concomitant increase in caspase 3 activity. To extend these findings we tested the functional effects of DHA and EPA, the two active omega-3 fatty acids of fish oil, on cultured MDA MB-231 cells. In agreement with our in vivo data, DHA and EPA treatment increased PTEN mRNA and protein expression and inhibited the phosphorylation of p65 subunit of NFkappaB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFkappaB DNA binding activity and NFkappaB-dependent transcription of Bcl-2 and Bcl-XL genes were also prevented by DHA and EPA treatment. Finally, we showed that PTEN expression significantly inhibited NFkappaB-dependent transcription of Bcl-2 and Bcl-XL genes. Taken together, our data reveals a novel signaling pathway linking the fish oil diet to increased PTEN expression that attenuates the growth promoting signals and augments the apoptotic signals, resulting in breast tumor regression.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18953692&dopt=ExternalLink
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PMID: 18953692 [PubMed - indexed for MEDLINE]16: Lipids Health Dis. 2008 Oct 13;7:36.
Rubin MG, Kim K, Logan AC.
Lasky Skin Clinic, 153 Lasky Drive, Suite 1, Beverly Hills, CA 90212, USA. markgrubinmd@aol.com
Acne vulgaris is a common skin condition, one that is associated with significant psychological disability. The psychological impairments in acne include higher rates of depression, anxiety, anger and suicidal thoughts. Despite a paucity of clinical research, patients with skin conditions and/or mental health disorders are frequent consumers of dietary supplements. An overlap may exist between nutrients that potentially have both anti-acne and mood regulating properties; examples include omega-3 fatty acids from fish oil, chromium, zinc and selenium. Here we report on five cases of acne treated with eicosapentaenoic acid and antioxidant nutrients. Self-administration of these nutrients may have improved inflammatory acne lesions and global aspects of well-being; the observations suggest a need for controlled trials.
Publication Types: Case Reports
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18851733&dopt=ExternalLink
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PMID: 18851733 [PubMed - indexed for MEDLINE]17: Pharm Res. 2008 Nov;25(11):2516-25. Epub 2008 Jul 12.
Davison Z, Dutkowski C, Gee JM, Nicholson RI, Heard CM.
Welsh School of Pharmacy, Cardiff University, CF10 3XF, Cardiff, UK.
PURPOSE: To determine the in vitro effects of simultaneously administered LY29400, PD98059, tamoxifen and eicosapentaenoic acid (EPA) on breast cancer cells, and determine their transcutaneous delivery. METHODS: Growth assays were performed on MCF-7 cells challenged with IC(50) and permeated concentrations of PD98059, LY294002 and tamoxifen firstly in isolation then combined. Permeation studies were performed using PD98059 and LY294002 (singly or simultaneously) in DMSO then fish oil, with enhancers. Immunocytochemical detection of phospho-MAPK, phospho-Akt, total COX-2 and Ki-67 was performed. RESULTS: When applied singly, fluxes of PD98059 and LY294002 were 0.09 +/- 0.008 and 0.14 +/- 0.045 microg cm(-2) h(-1), respectively; applied simultaneously, 0.18 +/- 0.045 and 0.49 +/- 0.051 microg cm(-2) h(-1). Permeated concentrations of PD98059 and LY294002 reduced growth to 13.78 +/- 0.63%. Fish oil plus 2.5% DMSO/ethanol allowed 5.96 +/- 0.9 and 7.7 +/- 1.2 microg cm(-2) of PD98059 and LY294002 to permeate after 48 h. CONCLUSIONS: PD98059 and LY294002 permeate excised skin at therapeutically useful rates, and also demonstrate growth inhibitory effects on MCF-7 cancer cells. Synergism was noted in co-transport across skin and activity against cancer cells. A formulation based on fish oil is potentially skin friendly; simultaneous permeation of EPA provides further anti-cancer action.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18622691&dopt=ExternalLink
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PMID: 18622691 [PubMed - indexed for MEDLINE]18: Nutrition. 2008 Mar;24(3):245-54.
Sierra S, Lara-Villoslada F, Comalada M, Olivares M, Xaus J.
Biomedicine Department, Puleva Biotech SA, Granada, Spain. molivares@puleva.es
OBJECTIVE: The omega-3 polyunsaturated fatty acids are involved in the modulation of the immune response. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) produced from dietary precursors may not be sufficient to match nutritional requirements and thus should be included in our diet. In this sense, the administration of higher amounts of DHA than of EPA in infant formulations is recommended. The aims of this work were to demonstrate that dietary administration of EPA or DHA to mice allows reaching similar tissue DHA levels and to compare their anti-inflammatory effects and mechanisms of action. METHODS: Balb/c mice were fed diets enriched with EPA or DHA for 3 wk. Twelve hours before sacrifice, a contact dermatitis was induced in the ears of the animals. Tissue fatty acid contents were determined. Cytokine and immunoglobulin concentrations were measured by enzyme-linked immunosorbent assay, and ears were collected to analyze local inflammatory effects. RESULTS: The DHA concentrations attained in tissues were similar to the two diets, whereas the EPA concentration increased only when the diet was enriched with this polyunsaturated fatty acid. Although EPA and DHA reduced ear inflammation, EPA reduced neutrophil infiltration in the ears more efficiently. EPA was associated with a greater reduction in the systemic macrophage inflammatory response and T-helper type 2 response and with increased interleukin-10 production. CONCLUSION: Similar levels of DHA in tissues are reached in mice fed an EPA- or a DHA-enriched diet. Dietary EPA and DHA show anti-inflammatory properties, but EPA appears to be more potent.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18312787&dopt=ExternalLink
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PMID: 18312787 [PubMed - indexed for MEDLINE]19: Free Radic Biol Med. 2008 Apr 1;44(7):1483-91. Epub 2008 Jan 26.
Vibet S, Goupille C, Bougnoux P, Steghens JP, Gore J, Maheo K.
Inserm E-0211, Nutrition, Croissance et Cancer; Universite Francois-Rabelais, Tours, France.
Docosahexaenoic acid (DHA, a lipid of marine origin) has been found to enhance the activity of several anticancer drugs through an oxidative mechanism. To examine the relation between chemosensitization by DHA and tumor cells antioxidant status, we used two breast cancer cell lines: MDA-MB-231, in which DHA increases sensitivity to doxorubicin, and MCF-7, which does not respond to DHA. Under these conditions, reactive oxygen species (ROS) level increased on anthracycline treatment only in MDA-MB-231. This was concomitant with a decreased cytosolic glutathione peroxidase (GPx1) activity, a crucial enzyme for protection against hydrogen and lipid peroxides, while major antioxidant enzyme activities increased in both cell lines in response to ROS. GPx-decreased activity was accompanied by an accumulation of glutathione, the GPx cosubstrate, and resulted from a decreased amount of GPx protein. In rat mammary tumors, when a DHA dietary supplementation led to an increased tumor sensitivity to anthracyclines, GPx1 activity was similarly decreased. Furthermore, vitamin E abolished both DHA effects on chemotherapy efficacy enhancement and on GPx1 inhibition. Thus, loss of GPx response to an oxidative stress in transformed cells may account for the ability of peroxidizable targets such as DHA to enhance tumor sensitivity to ROS-generating anticancer drugs.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18267129&dopt=ExternalLink
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PMID: 18267129 [PubMed - indexed for MEDLINE]20: Br J Dermatol. 2008 Apr;158(4):786-92. Epub 2008 Jan 30.
Koch C, Dolle S, Metzger M, Rasche C, Jungclas H, Ruhl R, Renz H, Worm M.
Allergy-Center-Charite, Department of Dermatology and Allergology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
BACKGROUND: The increasing prevalence of atopic eczema has been linked to the alteration of the Western diet, namely the reduced consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) and an increased omega-6 (n-6) PUFA intake. OBJECTIVES: The aim of the pilot study was to determine the efficacy of dietary n-3 PUFA docosahexaenoic acid (DHA) in patients with atopic eczema. METHODS: Fifty-three patients suffering from atopic eczema aged 18-40 years were recruited into this randomized, double-blind, controlled trial and received either DHA 5.4 g daily (n = 21) or an isoenergetic control of saturated fatty acids (n = 23) for 8 weeks. At weeks 0, 4, 8 and 20 the clinical outcome was assessed by the SCORAD (severity scoring of atopic dermatitis) index. IgE production and activation of peripheral blood mononuclear cells (PBMC) were analysed. Plasma fatty acids were measured by gas chromatography. RESULTS: DHA, but not the control treatment, resulted in a significant clinical improvement of atopic eczema in terms of a decreased SCORAD [DHA: baseline 37.0 (17.9-48.0), week 8 28.5 (17.6-51.0); control: baseline 35.4 (17.2-63.0), week 8 33.4 (10.7-56.2)]. A significant reduction of anti-CD40/interleukin 4-mediated IgE synthesis of PBMC was detected in the DHA group only. Supplementation led to a modulated activation status of PBMC in both groups. The DHA group showed an increase of plasma n-3 PUFA and a decrease in the n-6/n-3 PUFA ratio. CONCLUSIONS: Our data suggest that dietary DHA could be bioactive and might have a beneficial impact on the outcome of atopic eczema, but our results need to be confirmed in a larger study.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18241260&dopt=ExternalLink
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PMID: 18241260 [PubMed - indexed for MEDLINE]