Pinostilbene inhibits full-length and splice variant of androgen receptor in prostate cancer
“We tested whether pinostilbene can also affect expression of the ARv7 protein. Enzalutamide did not affect the protein or mRNA level of ARv7 in 22Rv1 (Fig. 5C and Supplementary Fig. 2D). With pinostilbene treatment, the expression of ARv7 decreased in a concentration-dependent manner in the 22Rv1 cell (Fig. 5C). Pinostilbene also decreased the mRNA expression of ARv7 (Fig. 5D). However, as shown in the full-length AR, the failure of ARv7 to be rescued when treated with MG132 shows that pinostilbene does not affect the protein stability of AR (Supplementary Fig. 3B). This suggests that pinostilbene has additional inhibitory effects on AR variant-dependent tumors such as Enz-resistant CRPC.“
Dietary pterostilbene for MTA1-targeted interception in high-risk premalignant prostate cancer
In conclusion, although the exact molecular mechanisms connecting MTA1 to epigenetic alterations, such as histone hypoacetylation leading to neoplasia, remain to be elucidated (57), the role of MTA1 per se as a prospective interceptive target for pterostilbene is undeniable. Pterostilbene, which is recognized as a potent anticancer agent (58) and exhibits good tolerability and no toxicity in humans when used in a dose up to 250 mg/day (34), should be urgently validated for clinical relevance in blocking prostate cancer progression in active surveillance subpopulation of patients.
Dietary stilbenes as modulators of specific miRNAs in prostate cancer
“In this review, we highlight the potential of metastasis-associated protein 1 (MTA1)-targeted anticancer and antitumor effects of three dietary stilbenes, namely resveratrol, pterostilbene, and gnetin C, for prostate cancer management. MTA1, an epigenetic reader and master transcriptional regulator, plays a key role in all stages of prostate cancer progression and metastasis. Stilbenes inhibit MTA1 expression, disrupt the MTA1/histone deacetylase complex, modulate MTA1-associated Epi-miRNAs and reduce MTA1-dependent inflammation, cell survival, and metastasis in prostate cancer in vitro and in vivo. Overall, the MTA1-targeted strategies involving dietary stilbenes may be valuable for effective chemoprevention in selected subpopulations of early stage prostate cancer patients and for combinatorial strategies with conventional chemotherapeutic drugs against advanced metastatic prostate cancer.“
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KocoPr
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Thanks for posting... another possible way to overcome resistance...always good stuff... I have been taking resveratrol for years. Will add pterostilbene when I get home...
Koko - The author of your second link, Anail S. Levenson, has apparently spent most/much of her career researching various stilbenes (with the majority of it focused on resveratrol), for their potential in treating both PCa and BCa. Curiously, her affiliation is listed as being at the "College of Veterinary Medicine, Long Island University, Brookville, NY, United States". Here is her professional profile:
I did a deep dive into her research history a week back and downloaded the Frontier's paper you linked. The first paper on Pinostilbene is more intriguing, esp. as it seems to act on AR and its splice variants. As it was published in Nature, it has quite a bit more credence than if published elsewhere.
BTW, a search of Levenson returns 54 research papers, re:
As anyone who has followed the research on resveratrol and other stilbenes, almost all research is done "in vitro" and at concentrations that are impossible to get from oral consumption. David Sinclair was a major promoter of resveratrol going back 10+ years. In fact, he nearly sabotaged his career becoming involved with companies that produced resveratrol while promoting its use. His focus has always been on longevity, so the research focus has been quite different from Levenson, with Sinclair mainly looking at the SIRT family of signaling proteins. While still supporting the use of resveratrol (he says he uses resveratrol powder in his morning yogurt to help with its bioavailablity, i.e, due to fat content of yogurt) his research is not, to my knowledge, on anything directly related to PCa.
Some years back, research indicated that Pterostilbene (think bluberries, etc.) and Fisetin (think strawberries) were shown to possibly be significantly better absorbed that resveratrol, i.e., in the case of Pterostilbene, on the order of 10X. Over the past 10 years or more, I have used various combos and dosages of all three - on an admittedly mostly random basis. Member mateobeach uses resveratrol+fisetin on a periodic "hit and run" treatment to help clear out senescent cells. (Please correct me if I have mischaracterized that, Paul.)
I am currently planning to find a reputable source of resveratrol and other stilbenes in powdered form, so I can add them to the plant powder mix I use in my daily smoothie. The smoothie usually includes some blueberries and strawberries, so it would be a combo that would hope to capture any whole plant synergies that might be absent in the extracts.
What we need is a company to develop a micronized or nano-enhanced form of the various stilbenes or stilbene derivatives that is super-absorbable. However, I'm not expecting that to happen anytime soon. In the meantime we can't help but piss much of it away.
Thanks for the post - and to Levenson for her career of continued research on our behalf.
another good reason to take resveratrol and combine it with NAC is to stop or minimize unmetabolized estrogens as they lead to DNA damage and to several hormone related cancers like PC, breast etc.
The late Ercole Cavelieri and present Elleanor Rogan have dedicated their whole career to the subject of dna damaging estrogens.
One of their recent papers was how to minimize these bad estrogens and Resveratrol and NAC can do this.
Wow excellent post n information. I’ve also used nmn pre surgery and prolonged the surgery itself but it wasn’t strong enough to kill or reduce the pca, so that’s when I decided to go ahead w the Rp. I have taken some combinations of nac, pyterstilbene and resveratrol on occasion but never really followed up.
So are u saying combo of rsvt n nac or pyterstilbine with nac…
There is a common mechanism leading to the initiation of many prevalent types of cancer. Cancer can be initiated by increased formation of reactive estrogen metabolites called catechol estrogen-3,4-quinones. If estrogen metabolism becomes unbalanced and significant amounts of these quinones arise, depurinating estrogen-DNA adducts are primarily formed, leading to cancer-causing mutations [10,11,12,13,14].
2. Initiation of Cancer
The pathway by which estrogens can cause cancer is shown in Figure 1. In this pathway, the estrogens estrone (E1) and estradiol (E2) are oxidized by cytochrome P450 (CYP)1B1 to the 4-catechol estrogens, 4-OHE1(E2) [18], which are further oxidized to the E1(E2)-3,4-quinones [E1(E2)-3,4-Q] by cytochrome P450 or peroxidases. Estrogen metabolism can be balanced or unbalanced in terms of the levels of catechol estrogen quinones formed. Normally, estrogen metabolism is balanced and low levels of E1(E2)-3,4-Q are formed, but when estrogen metabolism becomes unbalanced, higher levels of 4-OHE1(E2) and E1(E2)-3,4-Q are formed [11,12,13,14]; this has been demonstrated in the kidneys of Syrian golden hamsters [11], prostates of Noble rats [3,19], mammary glands of estrogen receptor knock-out (ERKO)/Wnt-1 mice [20], and breasts of women [12].
3. Prevention of Cancer by Inhibition of Estrogen-DNA Adduct Formation
Both resveratrol and NAC have been shown to inhibit the formation of depurinating estrogen-DNA adducts in cultured mammalian cells [30,31,32]. Resveratrol was found to inhibit the malignant transformation of the human MCF-10F breast epithelial cell line [31]. NAC was found to inhibit the malignant transformation of both MCF-10F and immortalized mouse mammary cells [33,55]. The two compounds work together additively to reduce the formation of depurinating estrogen-DNA adducts in MCF-10F cells treated with 4-OHE2 (Figure 4A) [30]. These results lay the foundation for investigating the ability of resveratrol and NAC to reduce estrogen-DNA adduct formation in humans as an approach to cancer prevention.
OK great, I have been using dim an estrogen blocker along w ashwaganda lately n psa dropped even further. I’ll def incorporate the rez, pytery n nac once again. Thanks for the breakdown..😁
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Nitric Oxide -- slows prostate cancer progression and PSA doubling time.
Why we add an AART drug to ADT?
ADT vacation versus Continuous