Grape Seed Proanthocyanidins Induce Apoptosis!!!!!!!!!!!

mumuka

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:shock: :shock: :shock:


Grape seed proanthocyanidins (GSP) have been shown to inhibit skin chemical carcinogenesis and photocarcinogenesis in mice. The mechanisms responsible for the anticarcinogenic effects of GSP are not clearly understood. Here, we report that treatment of JB6 C141 cells (a well-developed cell culture model for studying tumor promotion in keratinocytes) and p53+/+ fibroblasts with GSP resulted in a dose-dependent induction of apoptosis. GSP-induced (20–80 g/ml) apoptosis was observed by using immunofluorescence (27–90% apoptosis) and flow cytometry (18–87% apoptosis). The induction of apoptosis by GSP was p53-dependent because it occurred mainly in cells expressing wild-type p53 (p53+/+; 15–80%) to a much greater extent than in p53-deficient cells (p53-/-; 6–20%). GSP-induced apoptosis in JB6 C141 cells was associated with increased expression of the tumor-suppressor protein, p53, and its phosphorylation at Ser15. The antiapoptotic proteins, Bcl-2 and Bcl-xl, were downregulated by GSP, whereas the expression of the pro-apoptotic protein, Bax, and the levels of cytochrome c release, Apaf-1, caspase-9, and cleaved caspase 3 (p19 and p17) were markedly increased in JB6 C141 cells. The downregulation of Bcl-2 and upregulation of Bax were also observed in wild-type p53 (p53+/+) fibroblasts but was not observed in their p53-deficient counterparts. .These data clearly demonstrate that GSP-induced apoptosis is p53-dependent and mediated through the Bcl-2, Bax, and caspase 3 pathways.


http://www.pubmedcentral.nih.gov/articl ... id=1490319


Thats just great.
 

Pondle

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I take GSE... it's supposedly an aromatase inhibitor (stops testosterone from being converted into estrogen) and a potent antioxidant. If it can induce cell death in cancer cells that's good thing, right? My extremely limited knowledge of biochemistry prevents me from offering a more sophisticated critique!
 

Wash n' Gone

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I am with Pondle on this one. I don't pretend to properly understand the science on this, but surely the suppresion of carcinogens and cell death in tumours can only be a good thing? I don't see why this study should cause alarm :?
 

CCS

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how potent of an aromatase inhibitor is it? Can it be applied to the skin and absorbed into fat beath, like on gyno?
 

JonA

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how are u guys taking this grapeseed extract>?? i am really interested in taking it myself. Topically??? Orally??
 

Pondle

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There are two references to GSE as an aromatase inhibitor on PubMed. I have no idea what the ideal dose is, I just take 100mg/day usually. I'm guessing it's hardly the equivalent of Arimidex, but it makes me feel better. :)
 

JonA

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If i take it.. as an aromatase inhibitor, will the body become used to it or something.. then need more and more... and if i stop after a few years... will the body make even more eostragon than normal??
 

oyo

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Um no, this study means grape seed upregulates one of the pathways that kills off hair follicles. Not good.
 

michael barry

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oyo,

perhaps this is why the "regrowth" results from Revivogen aren't what one would expect from such a strong topical anti-androgen???????????????


Ive OFT wondered why the wrist hair on my right wrist has not regrown very well at all over TWO YEARS after putting revivogen on it. Perhaps this is why. Grape seed proanthocyandins inhibit Protien Kinease C, which is a negative growth factor in the dermal papilla, but if inhibiting PKC comes at the cost of mediated apoptosis eventually, it may be a better short term stimulant than a long term treatment and perhaps is best avoided.


Apple proanthocyandins B-2, also inhibit PKC and TGF-beta......................Ive yet to see a study linking them with apoptosis.


Ive seen a thing or two indicating SAGE, the oft-used essential oil, impedes TGF-mediated fibrosis in experiments.
 

oyo

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michael barry said:
oyo,

perhaps this is why the "regrowth" results from Revivogen aren't what one would expect from such a strong topical anti-androgen???????????????

Ive OFT wondered why the wrist hair on my right wrist has not regrown very well at all over TWO YEARS after putting revivogen on it. Perhaps this is why. Grape seed proanthocyandins inhibit Protien Kinease C, which is a negative growth factor in the dermal papilla, but if inhibiting PKC comes at the cost of mediated apoptosis eventually, it may be a better short term stimulant than a long term treatment and perhaps is best avoided.

Apple proanthocyandins B-2, also inhibit PKC and TGF-beta......................Ive yet to see a study linking them with apoptosis.

Ive seen a thing or two indicating SAGE, the oft-used essential oil, impedes TGF-mediated fibrosis in experiments.

I think keeping tissues healthy is a real balancing act. If things go off in any way, its a risk factor for cancer so the body kills it off; there are a number of apoptic pathways.

also doesn't grape seed have significant amount of resveratrol? i think resv increases p53 which increases BAX, which this study showed. I do think apple is better, it also has quercetin which had antifibrotic effects. although there is some in green tea too.

I'm really more interested in getting the follicles back to healthy equilibrium. the two main things we have now are reducing further damage (finasteride/dutasteride) and stiumulation through unrelated factors (minoxidil).

I don't think you can just offset a pro-apoptotic process with upregulating an unrelated pro-survival process. Although i'm not sure the science is really clear on all of this yet. But minoxidil is a good example, it is throwing a few pro-growth switches, but is undoing the ones that were fubar to begin with.

I really wish there was some bit of hair that was damaged by androgens other than the scalp, it makes it much harder to test things. And many of these substances are doing several things, and most of the studies don't really quantify it so we can compare hwat the net effect is.
 

CCS

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Re:

Pondle said:
I take GSE... it's supposedly an aromatase inhibitor (stops testosterone from being converted into estrogen) and a potent antioxidant. If it can induce cell death in cancer cells that's good thing, right? My extremely limited knowledge of biochemistry prevents me from offering a more sophisticated critique!

It is an aromatase inhibitor, which is why I do not put it on my head. I suspect GSE would grow body hair.
 

Pondle

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Re: Re:

collegechemistrystudent said:
It is an aromatase inhibitor, which is why I do not put it on my head. I suspect GSE would grow body hair.

I'm not sure if its proven effective in humans yet.

http://www.cbcrp.org/RESEARCH/PageGrant ... nt_id=4023

We have accrued 17 of the 24 women we intend to recruit for this trial, six of whom have completed the study on dose level 1 (50 mg/day of GSE). Aromatase inhibition assays for these blood specimens show no aromatase inhibitory effect at the 50mg/day dose level.

I thought I read something more recent about this study somewhere, and larger doses didn't have any effect either.
 

harold

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Lots of things that are shown to be beneficial to hair are not beneficvial to other cell types particularly cancerous cells. Lots of people are looking at green tea as an inhibitor of cancerous growth. You could find dozens of stdies showing apoptosis of cancer cells induced by EGCG. And yet EGCG is shown to be a hair growth promoting agent - at the end of the day that trumps everything else.
Studies in other cell types are nice to give a bit of support to a theory - to show that it is posssible that something similar is happening in the hair follicles we are interested in. But until those studies are actually done in hair then they remain suggestions only when study could show the exact opposite happens. BMPs grow bone but inhibit the growth of hair generally speaking. Minoxidil upregulates 5-alpha reductase but at the end of the day it has been shown time and time again to grow hair.
This is no big deal.
hh
 
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