Dietary fish oil inhibits human breast carcinoma growth: A function of increased lipid peroxidation

González, Michael J.; Schemmel, Rachel; Dugan, L. R.; Gray, J. I.; Welsch, Clifford W.

doi:10.1007/bf02536237

Cited by 159 publications

(90 citation statements)

References 24 publications

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“…Our results confirm those of earlier reports (Gonzalez et al, 1991(Gonzalez et al, , 1993) that supplementation of the high fish oil diet with a prooxidant, ferric citrate, suppresses breast cancer growth and increases lipid peroxidation products in human breast cancer growing in nude mice. Our original findings are as follows.…”

Section: Comparisons With Similar Past Researchsupporting

confidence: 92%

Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet

Hardman

Barnes²,

Knight³

et al. 1997

Br J Cancer

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Summary Lipid peroxidation products can be cytotoxic. Our objectives were (1) to use two pro-oxidants (iron and a pro-oxidative drug) to selectively increase lipid peroxidation in the implanted human breast tumours of mice consuming fish oil and (2) to kill the cancer cells without harming normal host tissues. The theoretical basis for selective cytotoxicity is that normal cells are better able to handle oxidative stress than cancer cells. Male athymic nude mice, consuming an AIN-76 diet, were injected s.c. with MDA-MB 231 human breast carcinoma cells. Three weeks later, all mice had palpable tumours, 3-10 mm in diameter, and diets were changed to modified AIN-76 diets containing 19% menhaden fish oil and 1% corn oil with or without supplemental 0.3% ferric citrate. After 2 weeks, half of the mice on each diet (19% fish oil with or without supplemental ferric citrate) were injected (three times per week for 2 weeks) with the ether-lipid drug edelfosine (ET-18-OCH3). The concentration of lipid peroxidation products in tumours (as measured by thiobarbituric acid-reactive substances, TBARS) was significantly increased by both ferric citrate and ET-18-OCH3. The TBARS in livers were not increased, nor was there evidence of other harmful side-effects to the host mice. The addition of iron enhanced tumour cell death whereas ET-1 8-OCH3 suppressed tumour cell mitosis. The use of iron supplementation combined with ET-18-OCH3 resulted in the slowest growth rate, lowest mitotic index, highest level of lipid peroxidation products and increased the cytotoxic index in tumours without detectable harm to the host. That iron supplementation increased tumour suppression beyond that expected from the increase in the concentration of TBARS in the tumour merits further investigation.

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Section: Comparisons With Similar Past Researchsupporting

confidence: 92%

Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet

Hardman

Barnes²,

Knight³

et al. 1997

Br J Cancer

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“…The increase in DNA synthesis rate was observed at high plasma concentrations of n-6 PUFAs (200-600 gM). In vivo studies have shown that PUFAs of the n-6 class may enhance both chemically induced and transplanted tumour development and that PUFAs of the n-3 class frequently exert (Gonzalez et al, 1993;Noguchi et al, 1995). Our short-term studies on growth-regulatory control by PUFAs does not account for long-term in vivo effects, and a clear correlation between in vivo and in vitro data can therefore not be expected.…”

Section: Discussionmentioning

confidence: 75%

Differential effect of polyunsaturated fatty acids on cell proliferation during human epithelial in vitro carcinogenesis: involvement of epidermal growth factor receptor tyrosine kinase

Mollerup

Haugen²

1996

Br J Cancer

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Summary Polyunsaturated fatty acids (PUFAs) have been implicated in tumour development and have been shown to influence cell proliferation in vitro. We report here that n-3 and n-6 PUFAs at concentration > 10 gM inhibited the proliferation of a human kidney epithelial cell line (2IHKE), which has retained phenotypic characteristics of normal kidney epithelial cells. In contrast, the proliferation was stimulated by n-3 and n-6 PUFAs at concentrations <10 gM under defined growth conditions. The stimulatory effect of n-3 and n-6 PUFAs was even more profound in the presence of EGF. In human kidney epithelial cell lines reflecting different stages of transformation (1IHKE and ITHKEras), the stimulatory effect was abrogated both in the presence and absence of EGF. Saturated fatty acids did not show any stimulatory effect on cell growth. The tyrosine kinase inhibitors genistein and tyrphostin-47 inhibited EGF-induced protein tyrosine phosphorylation dose-dependently in the 2IHKE cells, and abolished the growth stimulatory effect of docosahexaenoic acid (DHA). This indicates the involvement of EGF receptor tyrosine kinase activity in the observed increase in cell proliferation.

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“…13,14). Studies in cell culture and animal models have shown that DHA and eicosapentaenoic acid (20:5, n-3) inhibit tumorigenesis (15,16) and the growth of rodent tumors (17,18) and human breast cancer xenografts (19,20). Importantly, n-3 polyunsaturated fatty acids selectively inhibit tumor cell proliferation and are significantly less toxic towards normal cells (21,22).…”

Section: Introductionmentioning

confidence: 99%

Clioquinol and docosahexaenoic acid act synergistically to kill tumor cells

Ding

Liu

Vaught

et al. 2006

Molecular Cancer Therapeutics

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Clioquinol, an 8-hydroxyquinoline derivative (5-chloro-7-iodo-8-hydroxyquinoline) with antimicrobial properties, has recently been found to have cytotoxic activity towards human cancer cell lines at concentrations achieved by oral administration. This study was initiated to determine whether clioquinol could potentiate the antitumor effects of two drugs, doxorubicin and docosahexaenoic acid (DHA), believed to act in part via the generation of reactant oxidant species. At low micromolar concentrations, clioquinol had little effect upon cell viability and did not potentiate doxorubicin's cytotoxicity. Clioquinol significantly enhanced DHA's cytotoxic effects, an interaction that was shown to be synergistic by isobolographic analysis. Clioquinol exhibited a synergistic interaction with DHA in reducing nuclear factor-KB activity and inducing apoptosis, and the combination reduced the level of several molecules that promote cell survival, including Akt, p65, and Bcl-2. Interestingly, clioquinol neither induced lipid peroxidation itself nor increased peroxidation brought about by the addition of DHA. However, when cells were pretreated with antioxidant vitamin E, the synergism of clioquinol and DHA was blocked, indicating the essential role of lipid peroxidation for their action. These findings reveal a novel antitumor drug combination that synergistically targets major cell survival signaling pathways.

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Dietary fish oil inhibits human breast carcinoma growth: A function of increased lipid peroxidation

Cited by 159 publications

References 24 publications

Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet

Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet

Differential effect of polyunsaturated fatty acids on cell proliferation during human epithelial in vitro carcinogenesis: involvement of epidermal growth factor receptor tyrosine kinase

Clioquinol and docosahexaenoic acid act synergistically to kill tumor cells

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