Resveratrol & ARV7

[pjoshea13]

New study below.

AR-V7 is a truncated but active form of AR (androgen receptor). Its emergence is a common cause of resistance to Zytiga & Xtandi.

"First, we ectopically expressed ARV7 in PC3 cells, an AR-negative prostate cancer cell line, and demonstrated that resveratrol is capable of inhibiting ARV7 transcriptional activity by downregulating ARV7 protein levels."

"Next, we demonstrated that resveratrol is capable of downregulating the levels of the endogenously expressed ARV7 as well as AR target gene mRNAs in 22RV1 prostate cancer cells. Mechanistically, resveratrol downregulates ARV7 by enhancing ARV7 polyubiquitination and subsequent proteasome-mediated degradation."

Most resveratrol products are useless. Micronized products such as RevGenetics Nitro250 have good bioavailability. Perhaps useful when on Zytiga or Xtandi.

revgenetics.com/store/p-32-...

-Patrick

ncbi.nlm.nih.gov/pubmed/285...

Oncotarget. 2017 May 19. doi: 10.18632/oncotarget.18003. [Epub ahead of print]

Resveratrol enhances polyubiquitination-mediated ARV7 degradation in prostate cancer cells.

Wilson S1, Cavero L1, Tong D2, Liu Q2, Geary K1, Talamonti N1, Xu J2, Fu J3, Jiang J2, Zhang D1.

Author information

1

Department of Bio-Medical Sciences and Center for Chronic Diseases of Aging, Philadelphia College of Osteopathic Medicine, PA 19131, Philadelphia, USA.

2

Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

3

Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.

Abstract

Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide. In this study, we explored the effect of resveratrol on ARV7 transcriptional activity and the potential for development of resveratrol as a treatment for ARV7-positive prostate cancer. First, we ectopically expressed ARV7 in PC3 cells, an AR-negative prostate cancer cell line, and demonstrated that resveratrol is capable of inhibiting ARV7 transcriptional activity by downregulating ARV7 protein levels. Of note, resveratrol does not affect the mRNA levels of ARV7 nor its nuclear translocation. Next, we demonstrated that resveratrol is capable of downregulating the levels of the endogenously expressed ARV7 as well as AR target gene mRNAs in 22RV1 prostate cancer cells. Mechanistically, resveratrol downregulates ARV7 by enhancing ARV7 polyubiquitination and subsequent proteasome-mediated degradation. These findings suggest that resveratrol could be a potential treatment for ARV7-positive CPRC.

KEYWORDS:

ARV7; castration resistance; polyubiquitination; prostate cancer; resveratrol

PMID: 28589901 DOI: 10.18632/oncotarget.18003

[gusgold]

Patrick,

Pterostilbene is supposed to be way better than Reservatrol because it stays active for 3-hours as opposed to Resveratrols 25 minutes...I use both compounds...I wonder if high doses could prevent or delay CRPC

Gus

[ctarleton in reply to gusgold]

I regularly eat almonds, walnuts, and a little pure maple syrup on my oatmeal, or blueberries on my oatmeal, do those count?

Charles

[BigRich]

Patrick,

It is 5:00 AM and I haven't gone to sleep, yet. But if you have a gentic test and you don't have the ARV7 cell mutation; is not the above academic?

Rich

[pjoshea13 in reply to BigRich]

Rich,

If the therapy is working you don't have AR-V7 at that point. AR-V7 generally emerges as a response to therapy & becomes a cause of CRPC. Is it worthwhile looking for AR-V7 in CRPC? Perhaps resveratrol is useful with other shortened AR forms?

I have an issue with the concept of testing for AS-V7. It can be present at diagnosis, but in such small numbers that it is irrelevant at that point. Treatment will select for it, but until it becomes dominant, the therapy contines to have value.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

Not to have the side effects for a drug doomed to failure,

would it be best to know you have the cell mutation?

"but until it becomes dominant, the therapy contines to have value." Do you have a link that gives a timeline for failue with the mutation present before taking the drug? Does the test show the amount of mutation present?

Rich

[pjoshea13 in reply to BigRich]

Rich,

The test will not rule out later emergence of AR-V7.

Nor, I believe, will the test identify the percentage of PCa cells that are AR-V7.

If resveratrol can protect against against AR-V7, it seems prudent to use it throughout.

Note that Dr. Myers once said that resveratrol was beneficial in his CRPC patients. Perhaps this is why?

-Patrick

[BigRich]

Patrick,

Therefore, whether you take Zytiga or not it would be purdent to take reseveratrol to forestall ARV7 cell mutation! What is a good reseveratrol supplement, at what dosage?

Rich

[pjoshea13]

Myers recommends the product I mention in the post. 1/day is all I ever took.

-Patrick