Dietary n−3 PUFA alter colonocyte mitochondrial membrane composition and function

Chapkin, Robert S.; Hong, Mee Young; Yang, Fan; Davidson, Laurie A.; Sanders, Lisa; Henderson, Cara E.; Barhoumi, Rola; Burghardt, Robert C.; Turner, Nancy D.; Lupton, Joannè R.

doi:10.1007/s11745-002-0880-8

Cited by 85 publications

(60 citation statements)

References 36 publications

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“…Other mechanisms have been proposed to explain the cell growth inhibitory effect of EPA. Studies have indicated, for example, that dietary EPA and DHA can induce compositional changes in colonic mitochondrial membrane phospholipids that may, in turn, facilitate their inhibitory effect on cell proliferation as well as the induction of apoptosis in tumor cells (2,33). To our knowledge, this is the first study to demonstrate that PGE 3 produces antiproliferative effects on human nonsmall cell lung cancer cells.…”

Section: Discussionmentioning

confidence: 74%

Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells

Yang

Chan

Felix

et al. 2004

Journal of Lipid Research

104

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We investigated the formation and pharmacology of prostaglandin E 3 (PGE 3 ) derived from fish oil eicosapentaenoic acid (EPA) in human lung cancer A549 cells. Exposure of A549 cells to EPA resulted in the rapid formation and export of PGE 3. The extracellular ratio of PGE 3 to PGE 2 increased from 0.08 in control cells to 0.8 in cells exposed to EPA within 48 h. Incubation of EPA with cloned ovine or human recombinant cyclooxygenase 2 (COX-2) resulted in 13-and 18-fold greater formation of PGE 3 , respectively, than that produced by COX-1. Exposure of A549 cells to 1 M PGE 3 inhibited cell proliferation by 37.1% ( P Ͻ 0.05). Exposure of normal human bronchial epithelial (NHBE) cells to PGE 3 , however, had no effect. When A549 cells were exposed to EPA (25 M) or a combination of EPA and celecoxib (a selective COX-2 inhibitor), the inhibitory effect of EPA on the growth of A549 cells was reversed by the presence of celecoxib (at both 5 and 10 M). This effect appears to be associated with a 50% reduction of PGE 3 formation in cells treated with a combination of EPA and celecoxib compared with cells exposed to EPA alone. These data indicate that exposure of lung cancer cells to EPA results in a decrease in the COX-2-mediated formation of PGE 2 , an increase in the level of PGE 3 , and PGE 3 -mediated inhibition of tumor cell proliferation. 2)]. Epidemiologic studies have shown an inverse relationship between blood levels of n-3 fatty acids derived from fish oils and the risk of prostate and lung cancers (3-5). However, molecular mechanisms for the pharmacologic anticancer activity of EPA have not been fully elucidated. A number of studies have suggested that the anticancer activities of both EPA and DHA are associated with their ability to inhibit the synthesis of 2-series prostaglandins, especially prostaglandin E 2 (PGE 2 ) production [as reviewed in ref. (6)]. In contrast to DHA, however, EPA can actually function as a substrate for COX and result in the synthesis of unique 3-series prostaglandin compounds (7). To date, studies reporting the formation of 3-series prostaglandins by EPA have been performed using normal cells or tissues (8,9). Fischer and Weber (10), for example, provided the first evidence of in vivo formation of thromboxane A 3 and prostaglandin I 3 in humans fed fish oil. In addition, studies conducted in humans have shown that PGE 3 levels increased by ‫ف‬ 10-fold in urine after ingestion of cod liver oil (40 ml/day) for 12 weeks (11).In contrast to PGE 2 , the biological activity of PGE 3 has received little attention. The effect of PGE 3 on cell growth has been reported only in normal murine mammary epithelial (12) and 3T3 fibroblast cells (13). Both studies showed that PGE 2 and PGE 3 stimulated the growth of norAbbreviations: AA, arachidonic acid; BHT, butylated hydroxytoluene; calcein AM, acetoxymethyl ester of calcein; COX, cyclooxygenase; DAPI, 4 Ј ,6-diamidino-2-phenylindole; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LC/MS/MS, liquid chromatography/tandem mass sp...

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Section: Discussionmentioning

confidence: 74%

Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells

Yang

Chan

Felix

et al. 2004

Journal of Lipid Research

104

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“…The researchers found that the effects on colon cell proliferation depend on the type of fat (corn oil, fish oil or beef tallow) and fibre (pectin, cellulose) as well as of their combinations and reported several mechanisms of the effects observed. They showed that an important aspect of common DHA and butyrate effects is potentiation of the intrinsic mitochondrial apoptotic pathway 142 . Mitochondria also play a very important role in the maintenance of Ca2+ homeostasis, which is synergistically imbalanced by DHA and butyrate treatment, causing mitochondrial Ca2+ accumulation and peroxidation which triggers apoptosis in a p53-independent manner 143 .…”

Section: Interaction Of Dha With Butyratementioning

confidence: 99%

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Skender¹,

Vaculová²,

Hofmanová³

2012

BIOMED PAP

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Background. Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment. Results. From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family. Conclusion. Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

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“…58 Also, feeding of fish oil or purified n-3 fatty acid ethyl esters selectively increased EPA and DHA levels in the mitochondrial phosplolipids of colonocytes at the expense of n-6 fatty acids. 60 It has been shown that inhibition of colon carcinogenesis by DHA is mediated through the activation of retinoid X receptors (RXRs), a obligatory component of a large number of nuclear receptors, 61 suggesting n-3 PUFAs mediate growth inhibitory effects in the colon through the RXR subunit of nuclear receptor heterodimers. Members of the nuclear receptor superfamily are transcription factors that selectively regulate cell differentiation and proliferation.…”

Section: Possible Mode Of Action Of Types Of Dietary Fat In Colon Carmentioning

confidence: 99%

Omega‐3 fatty acids in colorectal cancer prevention

Reddy

2004

Intl Journal of Cancer

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Dietary n−3 PUFA alter colonocyte mitochondrial membrane composition and function

Cited by 85 publications

References 36 publications

Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells

Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Omega‐3 fatty acids in colorectal cancer prevention

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