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Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth.
Breast Cancer Res Treat 2009; 118(1):213-28BC

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 NFkappaB 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 omega-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 NFkappaB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFkappaB DNA binding activity and NFkappaB-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 NFkappaB-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.

Authors+Show Affiliations

Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18953692

Citation

Ghosh-Choudhury, Triparna, et al. "Fish Oil Targets PTEN to Regulate NFkappaB for Downregulation of Anti-apoptotic Genes in Breast Tumor Growth." Breast Cancer Research and Treatment, vol. 118, no. 1, 2009, pp. 213-28.
Ghosh-Choudhury T, Mandal CC, Woodruff K, et al. Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Breast Cancer Res Treat. 2009;118(1):213-28.
Ghosh-Choudhury, T., Mandal, C. C., Woodruff, K., St Clair, P., Fernandes, G., Choudhury, G. G., & Ghosh-Choudhury, N. (2009). Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Breast Cancer Research and Treatment, 118(1), pp. 213-28. doi:10.1007/s10549-008-0227-7.
Ghosh-Choudhury T, et al. Fish Oil Targets PTEN to Regulate NFkappaB for Downregulation of Anti-apoptotic Genes in Breast Tumor Growth. Breast Cancer Res Treat. 2009;118(1):213-28. PubMed PMID: 18953692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. AU - Ghosh-Choudhury,Triparna, AU - Mandal,Chandi C, AU - Woodruff,Kathleen, AU - St Clair,Patricia, AU - Fernandes,Gabriel, AU - Choudhury,Goutam G, AU - Ghosh-Choudhury,Nandini, Y1 - 2008/10/26/ PY - 2008/06/03/received PY - 2008/10/09/accepted PY - 2008/10/28/pubmed PY - 2010/1/27/medline PY - 2008/10/28/entrez SP - 213 EP - 28 JF - Breast cancer research and treatment JO - Breast Cancer Res. Treat. VL - 118 IS - 1 N2 - 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 NFkappaB 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 omega-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 NFkappaB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFkappaB DNA binding activity and NFkappaB-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 NFkappaB-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. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/18953692/Fish_oil_targets_PTEN_to_regulate_NFkappaB_for_downregulation_of_anti_apoptotic_genes_in_breast_tumor_growth_ L2 - https://doi.org/10.1007/s10549-008-0227-7 DB - PRIME DP - Unbound Medicine ER -