n-3 pufa and α-tocopherol control of tumor cell proliferation

Gm, Bartoli; Palozza, Paola; Marra, Giancarlo; Armelao, Franco; Franceschelli, Piergiorgio; Luberto, Chiara; Sgarlata, E; Piccioni, Elisabetta; Anti, M.

doi:10.1016/0098-2997(93)90011-2

Cited by 31 publications

(10 citation statements)

References 10 publications

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“…Decrease in cell proliferative activity was shown following dietary supplements of capsules containing fish-oil rich in n-3 FA, at a dosage of 4 g EPA and 2·2 g DHA/d for 6 months (Huang et al 1996). A similar response was noted with a dosage of 2·5 g EPA and DHA/d for 1 month in patients with colonic adenoma n-3 Fatty acids and breast cancer (Bartoli et al 1993;Anti et al 1994). Similar dosage levels can be used in a pilot clinical study of supplementary n-3 FA in premenopausal women at increased risk of BC.…”

Section: Proposed Clinical Studymentioning

confidence: 51%

n-3 Fatty acids and lipid peroxidation in breast cancer inhibition

Stoll

2002

Br J Nutr

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Long-chain n-3 fatty acids (FA) consistently inhibit the growth of human breast cancer (BC) cells both in culture and in grafts in immunosuppressed mice. Large cohort studies have, however, failed to confirm a protective effect for fish oils rich in n-3 FA against BC risk. The present review examines new evidence on biological mechanisms which may be involved in the inhibition of mammary carcinogenesis by long-chain n-3 FA, focusing on an apoptotic effect by its lipid peroxidation products. Dietary intake of n-3 FA leads to their incorporation into cell membrane lipids. Increased apoptosis in human BC cells following exposure to long-chain n-3 FA such as eicosapentaenoic and docosahexaenoic acids is generally ascribed to their inhibition of cyclooxygenase 2 which promotes mammary carcinogenesis. In addition however, longchain n-3 FA are particularly likely to activate peroxisome proliferator-activated receptor (PPAR)-g, a key regulator of lipid metabolism but also capable of modulating proliferative activity in a variety of cells including mammary cells. Expression of PPAR-g in the nucleus is activated by second messengers such as J series prostaglandins and the latter have been shown to cause apoptosis in vivo in explants of human BC cells in immunosuppressed mice. In mammary tumours, it is observed that long-chain FA not only increase apoptosis, but also increase lipid peroxidation, and the apoptotic effect can be reversed by antioxidants. The rationale for use of n-3 FA dietary supplements in counteracting BC progression needs to be tested clinically in a phase 2 pilot study, while at the same time, the effect on whole-body lipid peroxidation needs to be monitored. Dietary supplements of fish oil rich in n-3 FA are proposed for premenopausal women over the age of 40 years who are shown to be at increased BC risk. Biological markers in breast tissue of BC progression will be monitored, and observed changes related to serial plasma levels of isoprostanes as a measure of whole-body lipid peroxidation.

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Section: Proposed Clinical Studymentioning

confidence: 51%

n-3 Fatty acids and lipid peroxidation in breast cancer inhibition

Stoll

2002

Br J Nutr

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“…Two studies used EPA-FFA, whereas the others used a fish oil mixture containing EPA and DHA in varying proportions in either the ethyl ester or triglyceride form. In six of eight studies a 13–70% reduction in mucosal epithelial cell proliferation index was observed compared with the respective placebo group 64 93 94 96 97 100. In those studies comparing different doses of ω-3 PUFA, a dose-dependent reduction in the PI was observed 94 96…”

Section: Translational Studies Of Human Colorectal Biomarkers and ω-3mentioning

confidence: 92%

Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer

Cockbain

Toogood

Hull

2011

Gut

268

237

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Omega (u)-3 polyunsaturated fatty acids (PUFAs) are naturally occurring substances that are well tolerated and have been used extensively for the prevention of cardiovascular disease. More recently, u-3 PUFAs have been recognised to have anticancer activity. There is also evidence suggesting improved efficacy and/or tolerability of conventional cancer chemotherapy when administered with u-3 PUFAs. The purpose of this review is to (i) describe the mechanisms by which u-3 PUFAs are thought to have antineoplastic activity, (ii) review published preclinical and clinical studies that support anti-colorectal cancer activity and (iii) summarise current clinical trials investigating the potential therapeutic role(s) of u-3 PUFAs at different stages of colorectal carcinogenesis, from adenoma (polyp) prevention to treatment of established malignant disease and prevention of cancer recurrence.

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“…Prevention trials using n-3 supplements to reduce colorectal cancer risk have used cell proliferation in the colonic or rectal mucosa as an intermediate marker of cancer risk. A randomized double-blind trial found that administration of fish oil for 30 days to individuals with high risk for developing colon cancer reduced rectal mucosa proliferation to a level found in low risk population, with a concomitant increase in n-3 fatty acid and decrease in arachidonic acid in the rectal mucosa (121). A double-blind, crossover trial where healthy individuals were given a controlled basal diet supplemented with either fish oil or corn oil for 4 weeks showed that rectal cell proliferation, ornithine decarboxylase activity and PGE 2 release were significantly lower during the fish oil period than the corn oil period (122).…”

Section: Cancer Prevention and Treatment With N-3 Pufa Supplementsmentioning

confidence: 99%

Multi-targeted therapy of cancer by omega-3 fatty acids

2008

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Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are essential fatty acids necessary for human health. Currently, the Western diet contains a disproportionally high amount of n-6 PUFAs and low amount of n-3 PUFAs, and the resulting high n-6/n-3 ratio is thought to contribute to cardiovascular disease, inflammation, and cancer. Studies in human populations have linked high consumption of fish or fish oil to reduced risk of colon, prostate and breast cancer, although other studies failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of n-3 PUFAs on cancer in animal and cell culture models, has motivated the development of clinical interventions using n-3 PUFAs in the prevention and treatment of cancer, as well as for nutritional support of cancer patients to reduce weight loss and modulate the immune system. In this review, we discuss the rationale for using long-chain n-3 PUFAs in cancer prevention and treatment and the challenges that such approaches pose in the design of clinical trials.

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n-3 pufa and α-tocopherol control of tumor cell proliferation

Cited by 31 publications

References 10 publications

n-3 Fatty acids and lipid peroxidation in breast cancer inhibition

n-3 Fatty acids and lipid peroxidation in breast cancer inhibition

Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer

Multi-targeted therapy of cancer by omega-3 fatty acids

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