Grape Seed extract as AI?

Nutrition
1

Anthony Roberts e-mailed me this article a few weeks before REZ-V came out. Does anyone know how regular grapeseed extract compares to Rez-V?

Cancer Res. 2006 Jun 1;66(11):5960-7.

Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression.

Kijima I,
Phung S,
Hur G,
Kwok SL,
Chen S.

Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, California, USA.

Aromatase is the enzyme that converts androgen to estrogen. It is expressed at higher levels in breast cancer tissues than normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that have been shown in our laboratory to be potent inhibitors of aromatase. In this study, GSE was found to inhibit aromatase activity in a dose-dependent manner and reduce androgen-dependent tumor growth in an aromatase-transfected MCF-7 (MCF-7aro) breast cancer xenograft model, agreeing with our previous findings. We have also examined the effect of GSE on aromatase expression. Reverse transcription-PCR experiments showed that treatment with 60 mug/mL of GSE suppressed the levels of exon I.3-, exon PII-, and exon I.6-containing aromatase mRNAs in MCF-7 and SK-BR-3 cells. The levels of exon I.1-containing mRNA, however, did not change with GSE treatment. Transient transfection experiments with luciferase-aromatase promoter I.3/II or I.4 reporter vectors showed the suppression of the promoter activity in a dose-dependent manner. The GSE treatment also led to the down-regulation of two transcription factors, cyclic AMP-responsive element binding protein-1 (CREB-1) and glucocorticoid receptor (GR). CREB-1 and GR are known to up-regulate aromatase gene expression through promoters I.3/II and I.4, respectively. We believe that these results are exciting in that they show GSE to be potentially useful in the prevention/treatment of hormone-dependent breast cancer through the inhibition of aromatase activity as well as its expression.

2

JNG,

I’ve looked at the grape seed extract in the past and I’m looking at the full-text paper of the abstract below. Here is a quick breakdown of the current literature. There are compounds in GSE (not yet identified by these researchers) which as resveratrol was reported to do, inhibited both aromatase activity and expression. Having said that, they aren’t concerned with systemic activity (well, they are, but they’d rather have a lack thereof). Rather, these researchers are concerned with localized estrogen production (i.e., estrogen produced in breast tumors) as they should be. That however shouldn’t be confused with systemic suppression as is seen with the classic aromatase inhibitors (drugs). Now, that doesn’t mean that both can’t be seen (i.e., inhibition both locally and systemically) however for the time being, we only have data indicating a reduction of localized estrogen production.

In short, as these researchers say in their paper, they’re looking for a compound that will suppress aromatase activity locally (i.e., in breast tumor tissue) while allowing estrogen levels to remain the same in normal tissues. In short, they are looking for a tissue selective aromatase inhibitor.

Hope that helps.

[quote]JNG wrote:
Anthony Roberts e-mailed me this article a few weeks before REZ-V came out. Does anyone know how regular grapeseed extract compares to Rez-V?

Cancer Res. 2006 Jun 1;66(11):5960-7.

Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression.

Kijima I,
Phung S,
Hur G,
Kwok SL,
Chen S.

Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, California, USA.

Aromatase is the enzyme that converts androgen to estrogen. It is expressed at higher levels in breast cancer tissues than normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that have been shown in our laboratory to be potent inhibitors of aromatase. In this study, GSE was found to inhibit aromatase activity in a dose-dependent manner and reduce androgen-dependent tumor growth in an aromatase-transfected MCF-7 (MCF-7aro) breast cancer xenograft model, agreeing with our previous findings. We have also examined the effect of GSE on aromatase expression. Reverse transcription-PCR experiments showed that treatment with 60 mug/mL of GSE suppressed the levels of exon I.3-, exon PII-, and exon I.6-containing aromatase mRNAs in MCF-7 and SK-BR-3 cells. The levels of exon I.1-containing mRNA, however, did not change with GSE treatment. Transient transfection experiments with luciferase-aromatase promoter I.3/II or I.4 reporter vectors showed the suppression of the promoter activity in a dose-dependent manner. The GSE treatment also led to the down-regulation of two transcription factors, cyclic AMP-responsive element binding protein-1 (CREB-1) and glucocorticoid receptor (GR). CREB-1 and GR are known to up-regulate aromatase gene expression through promoters I.3/II and I.4, respectively. We believe that these results are exciting in that they show GSE to be potentially useful in the prevention/treatment of hormone-dependent breast cancer through the inhibition of aromatase activity as well as its expression.

[/quote]

3

I might be remembering things wrong, but doesn’t resveratrol come from grapes, either the skin or the seed?

4

[quote]vroom wrote:
I might be remembering things wrong, but doesn’t resveratrol come from grapes, either the skin or the seed?[/quote]

Yes, I think it is the skin.

Thats why red wine has more resveratrol than white wine as red is made with the skins for part of the process where as white wine isnt.

I am pretty sure that it is right. I am also sure that someone will correct me and make me look like a dick if I am wrong though.

5

Resveratrol comes from the skin. Interestingly some wine does not use the skin, so anyone attempting to gain the benefits of wine needs to be aware of this. Or they could load up on the Biotest sup and lose the only excuse to drink.

6

Oh I should add that white wine is made from fermenting grape juice, while red wine is made from fermenting grapes, so Helga is right that the white wines do not contain the skins, so their levels are much lower.

Different grapes have different levels of resveratrol, for example pinot noir grapes grown in New York, and Oregon have 4 times as much as California grown wine. Also this type of grape seems to produce something like 40 times the resveratrol produced by merlot and cabernet sauvignon grapes.

7

[quote]Cy Willson wrote:
JNG,

I’ve looked at the grape seed extract in the past and I’m looking at the full-text paper of the abstract below. Here is a quick breakdown of the current literature. There are compounds in GSE (not yet identified by these researchers) which as resveratrol was reported to do, inhibited both aromatase activity and expression. Having said that, they aren’t concerned with systemic activity (well, they are, but they’d rather have a lack thereof). Rather, these researchers are concerned with localized estrogen production (i.e., estrogen produced in breast tumors) as they should be. That however shouldn’t be confused with systemic suppression as is seen with the classic aromatase inhibitors (drugs). Now, that doesn’t mean that both can’t be seen (i.e., inhibition both locally and systemically) however for the time being, we only have data indicating a reduction of localized estrogen production.

In short, as these researchers say in their paper, they’re looking for a compound that will suppress aromatase activity locally (i.e., in breast tumor tissue) while allowing estrogen levels to remain the same in normal tissues. In short, they are looking for a tissue selective aromatase inhibitor.

Hope that helps.

[/quote]

Thanks Cy,

To follow up, do you know whether or not there is indeed Resveratrol in the seeds of grapes? And also, even though they are looking for a substance to locally inhibit aromatase, is it even possible to happen without a carry over to the rest of the body?

Thanks in advance.

Jon

8

[quote]JNG wrote:
Cy Willson wrote:
JNG,

I’ve looked at the grape seed extract in the past and I’m looking at the full-text paper of the abstract below. Here is a quick breakdown of the current literature. There are compounds in GSE (not yet identified by these researchers) which as resveratrol was reported to do, inhibited both aromatase activity and expression. Having said that, they aren’t concerned with systemic activity (well, they are, but they’d rather have a lack thereof). Rather, these researchers are concerned with localized estrogen production (i.e., estrogen produced in breast tumors) as they should be. That however shouldn’t be confused with systemic suppression as is seen with the classic aromatase inhibitors (drugs). Now, that doesn’t mean that both can’t be seen (i.e., inhibition both locally and systemically) however for the time being, we only have data indicating a reduction of localized estrogen production.

In short, as these researchers say in their paper, they’re looking for a compound that will suppress aromatase activity locally (i.e., in breast tumor tissue) while allowing estrogen levels to remain the same in normal tissues. In short, they are looking for a tissue selective aromatase inhibitor.

Hope that helps.

Thanks Cy,

To follow up, do you know whether or not there is indeed Resveratrol in the seeds of grapes? And also, even though they are looking for a substance to locally inhibit aromatase, is it even possible to happen without a carry over to the rest of the body?

Thanks in advance.

Jon

[/quote]

Hi Jon,

There may be trace quantities (I’m guessing but I’ve never seen mention of it) in the seed but as others have said, the skin is the primary source. Grape seeds on the other hand are known to contain the procyanidins which the paper also covers, which also have demonstrated anti-aromatase activity in vitro, but these are completely different from resveratrol.

I think it’s extremely interesting to note that so many of these compounds are found in the same fruit.

Yes, it’s possible to do so, it’s all in how the compound is distributed in the body and what the given dose may be. Though, you’re right, one will likely see at least some activity systemically, the broader idea would be to have a compound that would affect local activity maximally and systemic activity minimally.

But, I should also mention that the large advantage when seeking out a compound for these specific purposes is the over-expression of the enzyme (as in a breast tumor) in local tissue.

9

Thanks Cy, I appreciate you taking the time to answer my somewhat repetitive questions…

-Jon