Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity

L. A. deGraffenried, W. E. Friedrichs, L. Fulcher, G. Fernandes, J. M. Silva, J. M. Peralba, M. Hidalgo

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58 Scopus citations

Abstract

Background: Tamoxifen resistance is the underlying cause of treatment failure in a significant number of patients with breast cancer. Activation of Akt, a downstream mediator in the phosphatidylinositol 3-kinase (PI3K) signaling pathway has been implicated as one of the mechanisms involved in tamoxifen resistance. Breast cancers with heightened Akt activity are frequently associated with an aggressive disease and resistance to chemo- and hormone-therapy-induced apoptosis. Inhibition of PI3K restores apoptotic response to tamoxifen in hyperactive Akt cells. Therefore, agents that demonstrate Akt inhibitory properties are attractive therapeutic agents for the treatment of hormone-resistant breast cancer. n-3 fatty acids have proven to be potent and efficacious broad-spectrum protein kinase inhibitors. Materials and methods: In this study we demonstrate that the n-3 fatty acid, eicosapentaenoic acid (EPA), inhibits the kinase activity of Akt. Co-treatment with EPA renders breast cancer cells that overexpress a constitutively active Akt more responsive to the growth inhibitory effects of tamoxifen by approximately 35%. Conclusions: These findings suggest that EPA may be useful for the treatment of tamoxifen-resistant breast cancer cells with high levels of activated Akt and provide the rationale to test this hypothesis in the clinic.

Original languageEnglish (US)
Pages (from-to)1051-1056
Number of pages6
JournalAnnals of Oncology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2003

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Keywords

  • Akt
  • Tamoxifen
  • n-3 fatty acids

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

deGraffenried, L. A., Friedrichs, W. E., Fulcher, L., Fernandes, G., Silva, J. M., Peralba, J. M., & Hidalgo, M. (2003). Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity. Annals of Oncology, 14(7), 1051-1056. https://doi.org/10.1093/annonc/mdg291