flaxseed lignans inhibit estradiol induced growth, angiogenesis, and VEGF secretion

[Lani]

Unfortunately it was done in a her2- breast cancer cell line

If done in BT474--a her2+er+ breast cancer cell line it would be more applicable to those of you who are her2+ but also ER+

Clin Cancer Res. 2007 Feb 1;13(3):1061-7. Links
Flaxseed and Its Lignans Inhibit Estradiol-Induced Growth, Angiogenesis, and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Xenografts In vivo.

Bergman Jungestrom M,
Thompson LU,
Dabrosin C.
Authors' Affiliations: Divison of Oncology, Faculty of Health Sciences, University Hospital, Linkoping, Sweden and Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, which is crucial in cancer progression. We have previously shown that estradiol (E2) increases VEGF in breast cancer. Phytoestrogens are potential compounds in breast cancer prevention and treatment by poorly understood mechanisms. The main phytoestrogens in Western diet are lignans, and flaxseed is a rich source of the mammalian lignans enterodiol and enterolactone. EXPERIMENTAL DESIGN: In the present study, ovariectomized mice were treated with continuous release of E2. MCF-7 tumors were established and mice were fed with basal diet or 10% flaxseed, and two groups that were fed basal diet received daily injections with enterodiol or enterolactone (15 mg/kg body weight). RESULTS: We show that flaxseed, enterodiol, and enterolactone counteracted E2-induced growth and angiogenesis in solid tumors. Extracellular VEGF in vivo, sampled using microdialysis, in all intervention groups was significantly decreased compared with tumors in the basal diet group. Our in vivo findings were confirmed in vitro. By adding enterodiol or enterolactone, E2-induced VEGF secretion in MCF-7 cells decreased significantly without agonistic effects. The increased VEGF secretion by E2 in MCF-7 cells increased the expression of VEGF receptor-2 in umbilical vein endothelial cells, suggesting a proangiogenic effect by E2 by two different mechanisms, both of which were inhibited by the addition of lignans. CONCLUSIONS: Our results suggest that flaxseed and its lignans have potent antiestrogenic effects on estrogen receptor-positive breast cancer and may prove to be beneficial in breast cancer prevention strategies in the future.
PMID: 17289903 [PubMed - in process]

[jhandley]

Hi lani
If you look on the board you will find the article re. flaxseed muffins 1/day containing 25 g of flaxseed meal reduced her 2 overexpression by 70%; reduced tumour growth by 34 % and tumour cell suicide was 31 %.

Regards
Jackie

[Lani]

whether whole flaxseeds have beneficial or deleterious effects on her2+er+ breast cancer. The oil seems to have anti her2 effects, but the seed itself seems to have phytoestrogens which might stimulate growth. The closest cell line to approximate the tumors of her2+ER+patients' tumors is BT474.

This seemed to show that the lignans themselves had antiestrogenic effects on MCF7 (her2 negative) cell line cells--but whether that is counterbalanced by the phytoestrogens or whether the effect would be the same in BT474 does not seem to have been studied yet.

I would love to hear otherwise. Anyone?

[R.B.]

"The main phytoestrogens in Western diet are lignans, and flaxseed is a rich source of the mammalian lignans enterodiol and enterolactone."

Is the above not looking at phyto oestrogens?

The oil is high in omega three.

I will try and find some previous posts on the subject.

I know one's head begins to spin when one is reading so many technical articles on a huge range of diverse issues, particularly when as I am a lay person.

[Lani]

and that it has been for that reason that er+ patients have been warned off soy. Even if these are the main phytoestrogens, that does not mean they are the only or the most active phytoestrogens.

That is why my doncerns were whether the antihormonal effects of enterolactone and enterodiole working through the same mechanism of action as the other other phytoestrogens and negating their effect , is it a dose-dependent effect, is it only in rodents or also in humans, does it hold for her2+er+ cancers as well.

[Jean]

Lani,

I have been concerned to add flaxseed to my diet since I am so strongly
er+ 90%.....can you help clear up any of this mystery for me.

Is it safe for me to add this to my diet?


Jean

[Lani]

I really don't think they know yet. This was the closest I have found to a paper supporting the use of the whole seed including the phytoestrogens, but it was done with a her2- cell line (not in live people) and did not look at ALL the phytoestrogens in soy and how they all balance each other out ie, if some are more capable of stimulating the ER than others.

I seem to remember a conference on soy and cancer held in Chicago about a year and a half ago. I think it is held relatively regularly. Following studies they report and encouraging researchers to study her2+ cell lines like BT474 might speed up their finding an answer.

Sorry!

[R.B.]

More reading from previous posts

http://www.her2support.org/vbulletin...highlight=flax

http://www.her2support.org/vbulletin...ight=flax+seed

http://www.her2support.org/vbulletin...ight=flax+seed

If you search under flax seed or flaxseed using the search buton above you will find more.

RB

[TSund]

Has there ever been any proof that phytoestrogens ARE indeed bad for ER+?

I understand the theory, however I've also heard the hypotheses that phytoestrogens will actually help as while mildly estrogenic, they take the place on the receptors of much more dangerous forms of estrogen and lower the bodie's instinct to make more estrogen, which may be of the "bad" or "strong" variety.

I don't know which side has definitive evidence...

TRS

[R.B.]

There was a trial underway in Australia but I have not seen any more. I will try and find out.

RB

[Becky]

I use flax because its positive effects on Her2 are almost undisputable. I use it about 2X per week (the ground seed which would be more concerning if ER+ of which I am 50%). I use the oil too which I do not get the high lignan. That is not concerning. I use soy the way I used to before bc, if it came in some Chinese food we all ordered and shared (usually one meal or the soup has it). I was never a biggie on soy - maybe that was bad as I feel these foods are beneficial as a preventative to get bc. Once had, who knows but I believe flax is good so I will purposefully have it about 2X per week.