Abstract

We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA. What's new? A diet rich in fish oil can enhance the effects of tamoxifen in fighting cancer, but previous studies haven't been able to tease out at which stage of development the tumor is thwarted by the treatment. In this study, the authors gave mice a combination of fish oil and tamoxifen and sacrificed the mice at various stages of tumor development. They showed for the first time that fish oil combined with tamoxifen not only prevented the development of preneoplastic lesions, but also shrunk existing ones.

Original languageEnglish (US)
Pages (from-to)1549-1557
Number of pages9
JournalInternational Journal of Cancer
Volume134
Issue number7
DOIs
StatePublished - Apr 1 2014

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Omega-3 Fatty Acids
Tamoxifen
Fish Oils
Carcinogenesis
Breast
Diet
Corn Oil
Neoplasms
Sprague Dawley Rats
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Manni, Andrea ; Richie, John ; Xu, Haifang ; Washington, Sharlene ; Aliaga, Cesar ; Bruggeman, Richard ; Cooper, Timothy ; Prokopczyk, Bogdan ; Trushin, Neil ; Calcagnotto, Ana ; Das, Arunangshu ; Liao, Jiangang (Jason) ; El-Bayoumy, Karam. / Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis. In: International Journal of Cancer. 2014 ; Vol. 134, No. 7. pp. 1549-1557.
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title = "Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis",
abstract = "We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20{\%} corn oil [CO]) or a FO-rich diet (10{\%} FO + 10{\%} CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90{\%} of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA. What's new? A diet rich in fish oil can enhance the effects of tamoxifen in fighting cancer, but previous studies haven't been able to tease out at which stage of development the tumor is thwarted by the treatment. In this study, the authors gave mice a combination of fish oil and tamoxifen and sacrificed the mice at various stages of tumor development. They showed for the first time that fish oil combined with tamoxifen not only prevented the development of preneoplastic lesions, but also shrunk existing ones.",
author = "Andrea Manni and John Richie and Haifang Xu and Sharlene Washington and Cesar Aliaga and Richard Bruggeman and Timothy Cooper and Bogdan Prokopczyk and Neil Trushin and Ana Calcagnotto and Arunangshu Das and Liao, {Jiangang (Jason)} and Karam El-Bayoumy",
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Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis. / Manni, Andrea; Richie, John; Xu, Haifang; Washington, Sharlene; Aliaga, Cesar; Bruggeman, Richard; Cooper, Timothy; Prokopczyk, Bogdan; Trushin, Neil; Calcagnotto, Ana; Das, Arunangshu; Liao, Jiangang (Jason); El-Bayoumy, Karam.

In: International Journal of Cancer, Vol. 134, No. 7, 01.04.2014, p. 1549-1557.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis

AU - Manni, Andrea

AU - Richie, John

AU - Xu, Haifang

AU - Washington, Sharlene

AU - Aliaga, Cesar

AU - Bruggeman, Richard

AU - Cooper, Timothy

AU - Prokopczyk, Bogdan

AU - Trushin, Neil

AU - Calcagnotto, Ana

AU - Das, Arunangshu

AU - Liao, Jiangang (Jason)

AU - El-Bayoumy, Karam

PY - 2014/4/1

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N2 - We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA. What's new? A diet rich in fish oil can enhance the effects of tamoxifen in fighting cancer, but previous studies haven't been able to tease out at which stage of development the tumor is thwarted by the treatment. In this study, the authors gave mice a combination of fish oil and tamoxifen and sacrificed the mice at various stages of tumor development. They showed for the first time that fish oil combined with tamoxifen not only prevented the development of preneoplastic lesions, but also shrunk existing ones.

AB - We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA. What's new? A diet rich in fish oil can enhance the effects of tamoxifen in fighting cancer, but previous studies haven't been able to tease out at which stage of development the tumor is thwarted by the treatment. In this study, the authors gave mice a combination of fish oil and tamoxifen and sacrificed the mice at various stages of tumor development. They showed for the first time that fish oil combined with tamoxifen not only prevented the development of preneoplastic lesions, but also shrunk existing ones.

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