Theoretical study indicates the most practical natural anti-prostate cancer compound is grape seed extract

[Graham49]

B2G2, the most active ingredient of grape seed extract (GSE), can act as an agonist for PTEN. PTEN has a key role in suppressing PCa cells by applying phosphatase activity and inhibiting cell proliferation.

Investigation on the mechanisms by which the herbal remedies induce anti-prostate cancer activity: uncovering the most practical natural compound

Alireza PoustforooshORCID Icon, Sanaz Faramarz, Manica Negahdaripour, Burak TüzünORCID Icon & Hassan Hashemipour

Pages 3349-3362 | Received 21 Dec 2022, Accepted 04 May 2023, Published online: 17 May 2023

Cite this article doi.org/10.1080/07391102.20...

Abstract

Prostate cancer (PCa) is one of the most reported cancers among men worldwide. Targeting the essential proteins associated with PCa could be a promising method for cancer treatment. Traditional and herbal remedies (HRs) are the most practical approaches for PCa treatment. Here, the proteins and enzymes associated with PCa were determined based on the information obtained from the DisGeNET database. The proteins with a gene-disease association (GDA) score greater than 0.7 and the genes that have a disease specificity index (DSI) = 1 were selected as the target proteins. 28 HRs with anti-PCa activity as a traditional treatment for PCa were chosen as potential bioactive compounds. More than 500 compound-protein complexes were screened to find the top-ranked bioactives. The results were further evaluated using the molecular dynamics (MD) simulation and binding free energy calculations. The outcomes revealed that procyanidin B2 3,3′‐di‐O‐gallate (B2G2), the most active ingredient of grape seed extract (GSE), can act as an agonist for PTEN. PTEN has a key role in suppressing PCa cells by applying phosphatase activity and inhibiting cell proliferation. B2G2 exhibited a considerable binding affinity to PTEN (11.643 kcal/mol). The MD results indicated that B2G2 could stabilize the key residues of the phosphatase domain of PTEN and increase its activity. Based on the obtained results, the active ingredient of GSE, B2G2, could play an agonist role and effectively increase the phosphatase activity of PTEN. The grape seed extract is a useful nutrition that can be used in men’s diets to inhibit PCa in their bodies.

[cesanon]

Interesting. Does life extension carry it?

Does it have any other attributes?

[Graham49 in reply to cesanon]

Yes, Life Extension do sell it. I get from Piping Rock.

Here are are a few of the papers on trials with GSE, one PCa but mostly other conditions.

Abstract CT207: A phase II trial using grape seed extract for prostate cancer patients with non-metastatic PSA progression after local therapy

doi.org/10.1158/1538-7445.A...

“Taken together these results indicate that 300mg of daily GSE may improve PSA kinetics in pts with a rising PSA after maximum local therapy. This work was supported by NCI P30 CA46934 Cancer Center Support Grant, Cancer League of Colorado, the Writer Foundation, and the Barbara and Richard Gardner Fund for Prostate Cancer Research.”

The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials

doi.org/10.1016/j.jada.2011...

… In this meta-analysis of nine trials, participants receiving grape seed extract had a significant reduction in systolic blood pressure of −1.54 mm Hg and heart rate of −1.42 bpm, compared …

The effect of grape seed extract supplementation on oxidative stress and inflammation: a systematic review and meta‐analysis of controlled trials

First published: 09 June 2021

doi.org/10.1111/ijcp.14469

It appears that GSE supplementation can remarkably modulate the body's redox system, particularly through the inhibition of lipid peroxidation, but has neutral or mildly beneficial effects on inflammatory responses.

The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials

Corrigendum

Volume 36Issue 3Phytotherapy Research pages: 1413-1413 First Published online: March 23, 2022

doi.org/10.1002/ptr.6518

Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta-analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.

The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials

Medicine 95(33) e4247, August 2016. | DOI: 10.1097/MD.0000000000004247

Our findings demonstrate that grape seed extract exerted a beneficial impact on blood pressure, and this impact was more obvious in younger or obese subjects, as well as in patients with metabolic disorders. In view of the small sample size involved, we agree that confirmation of our findings in a large-scale, long-term, multiple-dose randomized controlled trial, especially among hypertensive patients is warranted.

Effects of grape seed extract on dyslipidaemia: a systematic review and dose–response meta-analysis of randomised controlled trials

DOI: doi.org/10.1017/S0007114520...

In conclusion, GSE supplementation seems to favourably affect serum levels of LDL as well as TAG levels, but it did not influence TC and HDL-cholesterol concentrations. However, given the limitations and small sample sizes of included studies, further investigations are needed to shed light on this issue. The take-home message of this study would be the recommendation to administer GSE as a secondary factor, along with medications, to control hyperlipidaemia.

[Lizzo30]

Here in UK we can only buy seedless grapes in our supermarkets it's ridiculous - are grapes seeded where you come from ?My husband has prostate cancer and we have red wine every day

[DesertDaisy in reply to Lizzo30]

You can purchase a grape seed extract supplement.

[Nwdx]

Thank you for posting, I just located some Resveratrol 500mg which is the only thing available where I am to start. Any studies comparing it?

[Maxone73]

Nice catch!

The problem is (as with every supplement) delivery. And that's what many researchers are working on, as many compounds (from curcumin to lycopene) are truly effective on cancer cells but we must find a way to get them to cancer cells in living human beings.

Let's hope that grape seed oral bioavailability is high enough to be effective for advance PCa. I am taking resveratrol that has also grape seed extract in it (incidentally, I was not looking for GSE) as I think that we all need help also to fight other diseases that we may encounter on our path!

In the positive side there are clinical trials already pointing in the right direction, which is always good!

[Graham49]

I agree but during the phase ll clinical trial a measurable effect was apparent even with a fairly low dose of GSE.

“The remaining 12 patients completed 12 months of follow-up. Mean post-treatment PSADT was 6.4 months. 9 patients met the endpoint of a PSADT increase of 30% or more. Taken together these results indicate that 300mg of daily GSE may improve PSA kinetics in pts with a rising PSA after maximum local therapy.”

[cujoe]

Graham - Having seen earlier research about grape seed extract (GSE) and PCa, I recently got the time to follow up on your post. And while there is substantial evidence of some efficacy for GSE in various PCa cell lines, this research paper from 2013 (linked below), clearly indicates that, as is the case in many supplement that show some degree of efficacy when used at non-achievable (via oral supplementation) real-world concentrations, we will need some commercial-grade super-concentration of B2G2 for this alternative treatment promise to be fulfilled. This comment from the paper succinctly summarizes the issue:

"The isolated yield of B2G2 is only about 0.3% (w/w) of the intact GSE. Thus isolating gram quantities involves cumbersome labor intensive and expensive chromatographic techniques." (emphasis added)

On the plus side, the paper tests (head-to-head) both a super-concentration of B2G2 from GSE and a synthesized form they created from scratch. They even describe the general process involved in the synthesis. Unfortunately, over these past many years reading research of a basic nature (now approaching 2 decades for me), the promises of such "basic" research (most often funded by goverment or institutions) seems never acted on, mostly due to the lack of interest by big pharma of paying for the clinical trial needed to advance the basic research; i.e., lab-produced, patentable research prevails. That said, the full synthesized formulation of B2G2 would seem to offer the possibility for patentable product, so one day maybe some enterprising company will take it on.

Procyanidin B2 3,3′′-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-B, Stat3, and AP1 Transcription Factors,Nutrition and Cancer, 2013.

sci-hub.st/10.1080/01635581...

As always, Thanks for your continuing efforts to find and share such research with our PCa community. The silver bullet we all seek may one day thus be found.

Stay S&W, Ciao - cujoe

[Nwdx in reply to cujoe]

"the promises of such "basic" research (most often funded by goverment or institutions) seems never acted on,"

Ahh... yes. There is no money in continued academia growing and receiving funding more studies if an solution is found. Last line of most research papers : " Further investigation / study is needed". Academia knows little or nothing usually about business, ime.