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Old 03-31-2005, 02:14 PM   #1
Christine MH
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Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice

"Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.

Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, Smorlesi A.

Laboratory of Tumor Immunology, Immunology Center, Research Department, Italian National Research Centers on Aging (INRCA), Ancona, Italy.

Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER-2/neu in tumoral mammary glands from Res-treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER-2/neu transgenic mice. The effects of Res were associated with downregulation of HER-2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL-2-induced NK activity nor the lymphocyte number and proliferation was modified in Res-supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER-2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER-2/neu expression and the induction of apoptosis in tumor cells. © 2005 Wiley-Liss, Inc."

Resveratrol occurs naturally in red wine (richest source), red grape juice, peanuts and Japanese bamboo (knotweed). Apparently it is also available as a supplement extracted from Japanese bamboo. At last a use for the wretched stuff, which apparently can be eaten. I think I'll stick to the grape juice.
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Old 04-01-2005, 05:42 AM   #2
*_Cara_*
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Good woman Christine.

I knew the odd glass of red wine had to be good for one.

I'll add in the peanuts but think I'll pass on the grape juice and the knotweed.
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Old 04-01-2005, 09:26 AM   #3
*_jeff_*
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But for er+ women...

I just want to throw into the mix that reservatrol is reported in some places (like the Sloan Ketterin herbs and supplements website) to have an estrogenic effect and should not be used by women with er+ tumors. I know that's a minority of women with her2+ tumors, but I still thought I'd mention it...

Best to all,
Jeff
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Old 04-01-2005, 09:41 AM   #4
Christine MH
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Good point, Jeff. SKBR3 (also known as SK-BR-3, and SKBR-3!) is ER-,PR-.
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Old 04-01-2005, 09:42 AM   #5
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Good point, Jeff. SKBR-3 is ER- and PR-. I don't know why, but it seems to be the HER2 cell line they study the most.
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Old 04-01-2005, 10:44 AM   #6
*_jeff_*
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Well, does it make sense on some level that most study on a her2 cell line would be on a er/pr- variant--Since the preponderance of her2+ tumors are er/pr negative?

It's been important for me to track this stuff because Rachel is er+ and pr (equivocal). So, while we're all for her using any supplements that might help, there have been a number of things (flax, ginger, milk thistle) that we've flagged because of their possible estrogenic effects.

I do wonder if the her2+/er+/pr- phenotype will start to get more attention since it's beginnign to look like it might be the one that explains a lot about the big ATAC trial and why Arimidex is coming out ahead in that one...

Best,
Jeff
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Old 04-02-2005, 09:20 PM   #7
KathySC
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Just another interesting article to add to the confusion about whether to take this supplement according to your ER status. According to this one, reservatrol does not stimulate ER positive cells. At least that is what I am taking from it.
Kathy
© 2002 The American Society for Nutritional Sciences J. Nutr. 132:3482S-3489S, November 2002



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Supplement: International Research Conference on Food, Nutrition & Cancer
Flavonoid Effects Relevant to Cancer1 ,2 ,3
Delia M. Brownson*, Nicolas G. Azios*, Brie K. Fuqua*, Su F. Dharmawardhane*,4 and Tom J. Mabry*

* Molecular Cell and Developmental Biology Section and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712



4To whom correspondence should be addressed. E-mail: surangi@mail.utexas.edu.



Flavonoids, such as daidzein and genistein, present in dietary plants like soybean, have unique chemical properties with biological activity relevant to cancer. Many flavonoids and polyphenols, including resveratrol in red wine and epigallocatechin gallate in green tea, are known antioxidants. Some of these compounds have estrogenic (and antiestrogenic) activity and are commonly referred to as phytoestrogens. A yeast-based estrogen receptor (ER) reporter assay has been used to measure the ability of flavonoids to bind to ER and activate estrogen responsive genes. Recently, estrogenic compounds were also shown to trigger rapid, nongenomic effects. The molecular mechanisms, however, have not been completely detailed and little information exists regarding their relevance to cancer progression. As a preliminary step toward elucidating rapid phytoestrogen action on breast cancer cells, we investigated the effect of 17-ß estradiol (E2), genistein, daidzein and resveratrol on the activation status of signaling proteins that regulate cell survival and invasion, the cell properties underlying breast cancer progression. The effect of these estrogenic compounds on the activation, via phosphorylation, of Akt/protein kinase B (Akt) and focal adhesion kinase (FAK) were analyzed in ER-positive and -negative human breast cancer cell lines. E2, genistein and daidzein increased whereas resveratrol decreased both Akt and FAK phosphorylation in nonmetastatic ER-positive T47D cells. In metastatic ER-negative MDA-MB-231 cells, all estrogenic compounds tested increased Akt and FAK phosphorylation. The inhibitory action of resveratrol on cell survival and proliferation is ER dependent. Therefore, all estrogenic compounds tested, including resveratrol, may exert supplementary ER-independent nongenomic effects on cell survival and migration in breast cancer cells.



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KEY WORDS: • estrogen signaling • phytoestrogen • breast cancer progression • FAK activity • Akt activity • phosphorylation • antioxidant activity
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Old 04-03-2005, 04:26 AM   #8
*_Christine MH_*
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Hi Kathy,

Thanks for that. If these two articles are right, then it sounds like resveratrol might be bad for Er-,Pr-,her2- cancers.

Take care,

Christine
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