Abstract

The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea-induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA-rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies.

Original languageEnglish (US)
Pages (from-to)322-330
Number of pages9
JournalCancer Prevention Research
Volume3
Issue number3
DOIs
StatePublished - Mar 1 2010

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Methylnitrosourea
Fish Oils
Omega-3 Fatty Acids
Tamoxifen
Carcinogenesis
Breast
Peroxisome Proliferator-Activated Receptors
Neoplasms
Breast Neoplasms
Oxidative Stress
Diet
Estrogen Receptor Modulators
Tumor Burden
Unsaturated Fatty Acids
Glutathione
Estrogens
Antioxidants
Hormones
Ligands
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{c0cc0b3ac9d341c7ac7a87ebd74c5bb2,
title = "The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-Methyl-N-Nitrosourea-Induced rat mammary carcinogenesis",
abstract = "The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea-induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA-rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies.",
author = "Andrea Manni and Haifang Xu and Sharlene Washington and Cesar Aliaga and Timothy Cooper and Richie, {John P.} and Richard Bruggeman and Bogdan Prokopczyk and Ana Calcagnotto and Neil Trushin and David Mauger and Verderame, {Michael F.} and Karam El-Bayoumy",
year = "2010",
month = "3",
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doi = "10.1158/1940-6207.CAPR-09-0173",
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volume = "3",
pages = "322--330",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
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}

The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-Methyl-N-Nitrosourea-Induced rat mammary carcinogenesis. / Manni, Andrea; Xu, Haifang; Washington, Sharlene; Aliaga, Cesar; Cooper, Timothy; Richie, John P.; Bruggeman, Richard; Prokopczyk, Bogdan; Calcagnotto, Ana; Trushin, Neil; Mauger, David; Verderame, Michael F.; El-Bayoumy, Karam.

In: Cancer Prevention Research, Vol. 3, No. 3, 01.03.2010, p. 322-330.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-Methyl-N-Nitrosourea-Induced rat mammary carcinogenesis

AU - Manni, Andrea

AU - Xu, Haifang

AU - Washington, Sharlene

AU - Aliaga, Cesar

AU - Cooper, Timothy

AU - Richie, John P.

AU - Bruggeman, Richard

AU - Prokopczyk, Bogdan

AU - Calcagnotto, Ana

AU - Trushin, Neil

AU - Mauger, David

AU - Verderame, Michael F.

AU - El-Bayoumy, Karam

PY - 2010/3/1

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N2 - The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea-induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA-rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies.

AB - The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea-induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA-rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies.

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