Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives

Wendel, Martina; Heller, Axel R.

doi:10.2174/1871520610909040457

Cited by 98 publications

(66 citation statements)

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“…A recent study by Schwerbrock and colleagues (40) showed that FO feeding had deleterious effects on the immune response to influenza infection, which was characterized by decreased CD8 + cytotoxic T lymphocytes, reduced neutrophils at the site of infection, and impaired natural killer cell cytotoxicity. Taken together, these observations indicate that whereas FO supplementation may be beneficial in lowering the risk of some cancers (41), FO may act differently in the etiology of infection-associated cancers.…”

Section: Discussionmentioning

confidence: 78%

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

et al. 2010

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Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this study is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3−/− mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8 + cell frequency and diminished CD69 expression on CD4 + and CD8 + T-cell populations. Mice consuming DFO also exhibited higher FoxP3 + CD25 + CD4 + T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded that DFO-fed mice may be less equipped to mount a successful response to H. hepaticus infection, increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD.

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Section: Discussionmentioning

confidence: 78%

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

et al. 2010

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“…At least partly due to their antiinflammatory properties, omega-3 (w-3) fatty acids are proposed to have anticancer actions (2). Indeed, once incorporated into biologic membranes, w-3 fatty acids are converted into lipid mediators, named eicosanoids, with anti-inflammatory properties via a succession of enzymes: desaturase, elongase, cyclooxygenase, and lipoxygenase (3).…”

Section: Introductionmentioning

confidence: 99%

Prostatic and Dietary Omega-3 Fatty Acids and Prostate Cancer Progression during Active Surveillance

Moreel

Allaire

Léger

et al. 2014

Cancer Prevention Research

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The association between omega-3 (w-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary w-3 fatty acids intake and the w-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue w-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue w-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer. Cancer Prev Res; 7(7); 766-76. Ó2014 AACR.

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“…Increasing evidence from animal and in vitro studies indicates that fatty acids, especially the long-chain polyunsaturated fatty acids (PUFAs), 2 affect carcinogenesis (1). n-3 PUFAs inhibit the growth of tumor cells both in vivo and in vitro (2,3), decrease metastasis and cachexia (4,5), and increase the cytotoxic effects of some chemotherapeutic agents (6), although the results are not always consistent (7,8).…”

mentioning

confidence: 99%

“…n-3 PUFAs inhibit the growth of tumor cells both in vivo and in vitro (2,3), decrease metastasis and cachexia (4,5), and increase the cytotoxic effects of some chemotherapeutic agents (6), although the results are not always consistent (7,8). In addition, n-3 PUFAs reduce cell proliferation and induce differentiation and apoptosis in hepatocarcinoma and leukemia cells (9 -12).…”

mentioning

confidence: 99%

“…Although not completely known, several molecular mechanisms whereby n-3 PUFAs may modify the carcinogenic process have been proposed. These include alteration in cell membrane composition and function, modulation of mitochondrial calcium homeostasis, suppression of the biosynthesis of proinflammatory molecules, influence on signal transduction, alteration of hormone-stimulated cell growth, inhibition of angiogenic mediators, production of free radicals and reactive oxygen species, and influence on transcription factor activity and gene expression (2,(13)(14)(15)(16)(17).…”

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confidence: 99%

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Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

Ceccarelli

Racanicchi

Martelli

et al. 2011

Journal of Biological Chemistry

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Polyunsaturated fatty acids (PUFAs) inhibit proliferation and induce differentiation in leukemia cells. To investigate the molecular mechanisms whereby fatty acids affect these processes, U937 leukemia cells were conditioned with stearic, oleic, linolenic, ␣-linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids. PUFAs affected proliferation; eicosapentaenoic acid (EPA) was the most potent on cell cycle progression. EPA enhanced the expression of the myeloid lineage-specific transcription factors CCAAT/enhancer-binding proteins (C/EBP␤ and C/EBP␦), PU.1, and c-Jun, resulting in increased expression of the monocyte lineage-specific target gene, the macrophage colony-stimulating factor receptor. Indeed, it is known that PU.1 and C/EBPs interact with their consensus sequences on a small DNA fragment of macrophage colony-stimulating factor receptor promoter, which is a determinant for expression. We demonstrated that C/EBP␤ and C/EBP␦ bind the same response element as a heterodimer. We focused on the enhanced expression of C/EBP␦, which has been reported to be a tumor suppressor gene silenced by promoter hypermethylation in U937 cells. After U937 conditioning with EPA and bisulfite sequencing of the ؊370/؊20 CpG island on the C/EBP␦ promoter region, we found a site-specific CpG demethylation that was a determinant for the binding activity of Sp1, an essential factor for C/EBP␦ gene basal expression. Our results provide evidence for a new role of PUFAs in the regulation of gene expression. Moreover, we demonstrated for the first time that re-expression of the tumor suppressor C/EBP␦ is controlled by the methylation state of a site-specific CpG dinucleotide.

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Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives

Cited by 98 publications

References 0 publications

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

Prostatic and Dietary Omega-3 Fatty Acids and Prostate Cancer Progression during Active Surveillance

Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

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