Opposing Effects of n-6 and n-3 Polyunsaturated Fatty Acids on Pancreatic Cancer Growth

Funahashi, Hitoshi; Satake, Makoto; Hasan, Sascha; Sawai, Hirozumi; Newman, Robert A.; Reber, Howard A.; Hines, Oscar J.; Eibl, Guido

doi:10.1097/mpa.0b013e31815ccc44

Cited by 76 publications

(63 citation statements)

References 41 publications

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“…It is known that n-3 PUFAs and n-6 PUFAs follow similar metabolic pathways, leading to the formation of two arrays of eicosanoids that have opposite functions (Das, 2006a;2006b;Funahashi et al, 2008). PUFAs of n-3 series seem to possess anticancer actions and have been shown to inhibit cell proliferation and induce apoptosis, whereas the products of n-6 PUFAs are believed to enhance cancer cell proliferation (Larsson et al, 2004;Kelavkar et al, 2006a).…”

Section: Discussionmentioning

confidence: 99%

“…In general, it is believed that n-6 fatty acids are unhelpful in cancer prevention and therapy, whereas n-3 fatty acids are beneficial. This is because n-6 forms precursors of several pro-inflammatory eicosanoids, whereas products formed from n-3 are much less pro-inflammatory (Das, 2006a;2006b;Funahashi et al, 2008). When n-6 and n-3 fatty acids were tested for their effects on cancer cells, it was found that n-3 PUFAs were much more effective in inhibiting cancer cell growth compared with n-6 PUFAs (Ip, 1993;Klurfeld and Bull, 1997;Kumar and Das, 1997;Chapkin et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

et al. 2010

J. Zhejiang Univ. Sci. B

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Polyunsaturated fatty acids (PUFAs) possess anti-cancer action both in vitro and in vivo. In the present study, we detected cell viability with methyl thiazolyl tetrazolium (MTT) assay and cell membrane permeability with propidium iodide (PI) fluorescence dyeing, and calculated cell membrane fluidity change as fluorescence anisotropy. Fatty acid content in cells was measured by gas chromatography/mass spectroscopy (GC/MS), and the relationship between fatty acid composition and cell viability was studied. We observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (≥300 µmol/L), while low concentrations (100-200 µmol/L) seemed to promote cell proliferation. Analyses of cell membrane permeability, cell membrane fluidity, and cell fatty acid composition suggested that the anti-cancer action of LA could be related to changes in the ratio of n-6 to n-3 PUFAs. We observed that pre-incubation of cancer cells with 100 µmol/L LA for 24 h enhanced cell sensitivity to the cytotoxic action of LA, whereas undifferentiated cell line LoVo seemed to have a distinct path in LA-induced death. These results showed that one of the mechanisms by which supplementation of LA induces cancer cell death could be altering the ratio of n-6/n-3 PUFAs, and this may be related to cell differentiation status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

et al. 2010

J. Zhejiang Univ. Sci. B

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“…It has been demonstrated that the effect of LC n-3 PUFA on pancreatic function may be mediated by inhibition of PG and pro-inflammatory cytokine synthesis 238,239 . Particularly, the anticarcinogenic properties of LC n-3 PUFA, which are mainly attributed to altered PG formation due to COX-2 inhibition, may prove beneficial in pancreatic cancer 240 . Fish oil in total parenteral nutrition improved patient recovery and indices of pancreatic and hepatic function in postoperative cancer patients 231,241 .…”

Section: Critically Ill Patients Cancer and Other Chronic Diseasesmentioning

confidence: 99%

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

Kremmyda¹,

Tvrzická²,

Staňková³

et al. 2011

BIOMED PAP

150

134

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Background. This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health.Results. The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders.Conclusion. Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.humans. Thus, these FA may be characterised as conditionally essential depending on EFA availability. Genetic variation in human desaturase genes affects FA metabolism, plasma lipid profiles, and risk of disease development [5][6][7] . Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day 8 , especially for pregnant women and those of reproductive age. Rich sources of LC n-3 PUFA are fish oils and the flesh of oily fish, whereas non-oily (white) fish contain them but in lower amounts.Long-chain PUFA with 18-20 carbon atoms, including EPA and AA, are precursors of eicosanoids (prostaglandins, leucotrienes and thromboxanes), which have a broad scale of regulatory, autocrine and paracrine effects. Long-chain PUFA with 20 and 22 carbon atoms are precursors of autacoids -resolvins (resolution phase interaction products), lipoxins and neuroprotectins 9 . FA are also ligands of nuclear receptors which take part in the subcellular control of metabolic pathways. Covalent modification of proteins by FA acylation enables their incorporation into membranes. Hydroxy FA are activators of some nuclear factors and are responsible for the expression of proinflammatory cytokines (interleukin (IL)-1,

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“…Thus, HIF-1 expression increases cell viability [17]. According to a recent study, n6PUFAs increase prostaglandin E2 (PGE2) in pancreatic cancer cells and thereby stimulate HIF-1α expression and increase cell viability [18]. In contrast, n3PUFAs increase prostaglandin E3 (PGE3) and thus inhibit HIF-1α expression and decrease cell viability [18].…”

Section: Introductionmentioning

confidence: 99%

Four types of fatty acids exert differential impact on pancreatic cancer growth

Yu¹,

Liu²,

Duan³

et al. 2015

Cancer Letters

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Opposing Effects of n-6 and n-3 Polyunsaturated Fatty Acids on Pancreatic Cancer Growth

Cited by 76 publications

References 41 publications

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

Four types of fatty acids exert differential impact on pancreatic cancer growth

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