HER2 Support Group Forums - View Single Post - The Plant Feverfew and Resistance to Tamoxifen

Rich66 · 02-28-2010, 10:03 AM

As an added bonus, I suspect you have fewer fevers

Going from the green Earth to the blue sea, Fish oil seems to inhibit similar targets:

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

L. A. deGraffenried 1 +§,

FULL TEXT

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.

Breast Cancer Res Treat. 2009 Nov;118(1):213-28. Epub 2008 Oct 26.
Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth.

Ghosh-Choudhury T, Mandal CC, Woodruff K, St Clair P, Fernandes G, Choudhury GG, Ghosh-Choudhury N.
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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.

PMID: 18953692 [PubMed - indexed for MEDLINE]

02-28-2010, 10:03 AM	#2
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: The Plant Feverfew and Resistance to Tamoxifen As an added bonus, I suspect you have fewer fevers Going from the green Earth to the blue sea, Fish oil seems to inhibit similar targets: Eicosapentaenoic acid restores tamoxifen sensitivity in breast cancer cells with high Akt activity L. A. deGraffenried 1 +§, W. E. Friedrichs 1 §, L. Fulcher 1, G. Fernandes 1, J. M. Silva 1, J.-M. Peralba 2 and M. Hidalgo 2 FULL TEXT 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. Breast Cancer Res Treat. 2009 Nov;118(1):213-28. Epub 2008 Oct 26. Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Ghosh-Choudhury T, Mandal CC, Woodruff K, St Clair P, Fernandes G, Choudhury GG, Ghosh-Choudhury N. Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. 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. PMID: 18953692 [PubMed - indexed for MEDLINE] __________________ Mom's treatment history (link)