Fish oil targets PTEN to regulate NFκB for downregulation of anti-apoptotic genes in breast tumor growth

Triparna Ghosh-Choudhury, Chandi C. Mandal, Kathleen Woodruff, Patricia St Clair, Gabriel Fernandes, Goutam G. Choudhury, Nandini Ghosh-Choudhury

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The molecular mechanism for the beneficial effect of fish oil on breast tumor growth is largely undefined. Using the xenograft model in nude mice, we for the first time report that the fish oil diet significantly increased the level of PTEN protein in the breast tumors. In addition, the fish oil diet attenuated the PI 3 kinase and Akt kinase activity in the tumors leading to significant inhibition of NFκB activation. Fish oil diet also prevented the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in the breast tumors with concomitant increase in caspase 3 activity. To extend these findings we tested the functional effects of DHA and EPA, the two active ω-3 fatty acids of fish oil, on cultured MDA MB-231 cells. In agreement with our in vivo data, DHA and EPA treatment increased PTEN mRNA and protein expression and inhibited the phosphorylation of p65 subunit of NFκB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFκB DNA binding activity and NFκB-dependent transcription of Bcl-2 and Bcl-XL genes were also prevented by DHA and EPA treatment. Finally, we showed that PTEN expression significantly inhibited NFκB-dependent transcription of Bcl-2 and Bcl-XL genes. Taken together, our data reveals a novel signaling pathway linking the fish oil diet to increased PTEN expression that attenuates the growth promoting signals and augments the apoptotic signals, resulting in breast tumor regression.

Original languageEnglish (US)
Pages (from-to)213-228
Number of pages16
JournalBreast Cancer Research and Treatment
Volume118
Issue number1
DOIs
StatePublished - Nov 1 2009

Keywords

  • Apoptotic signal
  • Breast tumor growth
  • DHA
  • EPA
  • NFκB
  • PTEN

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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