I really didn't want to get into a citations war where the results of one paper are immediately challenged by someone posting the results of a different or even contradictory study. I guess we all must make decisions as to which information we want to believe. Yes, cherry-picking, if you will. That said, I will cite below why I have decided to include Ursolic Acid in my daily regimen. If someone disagrees, fine, but as I have stated above, I won't participate in a “citation war.” You guys make your own decisions, but please remember that I am the messenger, not the message. Any disagreements, please direct them to the authors of the paper to let them respond.This disease has taken its toll, unfortunately, in defining who I am and I don't like it, but with many of us it is a matter of life and death, so in addition to the drugs we take courtesy of Big Pharma, most of us try, no matter how feeble (and laughable to some of our more learned members), with the goal of modestly affecting our conditioon in a positive way.
Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina.
ABSTRACT
Extracts of Prunella vulgaris have been shown to exert antiestrogenic effects. To identify the compounds responsible for these actions, we isolated the constituents of P. vulgaris and tested their individual antiestrogenic effects. Rosmarinic acid, caffeic acid, ursolic acid (UA), oleanolic acid, hyperoside, rutin and betulinic acid (BA) were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae). Among these constituents, UA and BA showed significant antiestrogenic effects, measured as a decrease in the mRNA level of GREB1, an estrogen-responsive protein; the effects of BA were stronger than those of UA. UA and BA were capable of suppressing estrogen response element (ERE)-dependent luciferase activity and expression of estrogen-responsive genes in response to exposure to estradiol, further supporting the suppressive role of these compounds in estrogen-induced signaling. However, neither UA nor BA was capable of suppressing estrogen signaling in cells ectopically overexpressing estrogen receptor α (ERα). Furthermore, both mRNA and protein levels of ERα were reduced by treatment with UA or BA, suggesting that UA and BA inhibit estrogen signaling by suppressing the expression of ERα. Interestingly, both compounds enhanced prostate-specific antigen promoter activity. Collectively, these findings demonstrate that UA and BA are responsible for the antiestrogenic effects of P. vulgaris and suggest their potential use as therapeutic agents against estrogen-dependent tumors. Kim HI1, Quan FS2, Kim JE1, Lee NR1, Kim HJ1, Jo SJ1, Lee CM1, Jang DS3, Inn KS4.
mRNA which can be fragmented and faces the problem of being cleaved at weak spots [Reactive Sites]. Single Strand RNA is very much weaker in its molecular structure, than than the double helix[Double Strand] DNA.and has been implicated in regulating androgen receptors
Also when looking at estrogen receptors, ER-Alphas are in the intercellular structure of the PCa cell while the ER-Betas are on the membrane of the PCa Cell. There would be more concern as to actions allowing more androgens, specifically E2, access to the ER-Alphas, than the membrane ER-Betas.
If if you can prevent protein encoding for the growth of PCa cells, and keep Estradiol from the ER-Alphas, and some of the ER-Betas---the RNA will not have which to carry to the PCa cell Receptors---since Estradiol is the androgen most likely to do the most harm.
“The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. Prostate. 2018 Jan;78(1):2-10. doi: 10.1002/pros.23446. Epub 2017 Nov 2. Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.”
Written by
Kuanyin
To view profiles and participate in discussions please or .
In fact, activating the estrogen alpha receptor (ERα) has been found to slow down prostate cancer. In fact, a drug called Capesaris has been developed that is an ERα AGONIST (meaning it activates the estrogen alpha receptor). Capesaris has been shown in clinical trials to be effective even after Lupron fails:
So, "inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid" would make one's prostate cancer WORSE instead of better. Just because a drug is available without an Rx doesn't make it safe or effective. It should scare you that you are taking it.
While Capesaris is not yet available, estrogen patches are.
"Estradiol receptor α expression is significantly associated with high Gleason score and poor survival in PC patients (36), while the expression of ERβ was found decreased or lost in PC samples"
Regarding betulinic acid, I obtain this from chaga mushroom.
No. Clinical trials trump mouse studies. Capesaris,as you see WAS effective in slowing progression. Estrogen was the first drug ever found effective against PC and patches are in clinical trials now.
If betulinic acid is also an estrogen alpha receptor blocker, it's an equally bad idea for someone with prostate cancer to take it.
Kuanyin & you are writing about two different things.
For men on ADT, ERα in PCa cells becomes largely irrelevant.
You say "activating the estrogen alpha receptor (ERα) has been found to slow down prostate cancer". But you are confusing ERα activation & castration. Capesaris is better than Lupron at lowering free testosterone [T]. It doesn't do that by selectively binding to PCa ERα & activating it.
Capesaris, a synthetic nonsteroidal estrogen with a structure similar to DES, might well be an agonist for PCa ERα, but in the absence of T, the androgen receptor [AR] cannot be activated. The issues with ERα occur only when it is able to co-opt AR for proliferation.
I'm sorry but you got that wrong. " ERα in PCa cells becomes largely irrelevant." Not so, as the Capesaris studies prove. Capesaris DOES bind with with the PCa ERα activates it . That's EXACTLY how it works - it's a ERα agonist. That's exactly what an agonist means. The ERα does not "co-opt" the androgen receptor- they are totally separate receptors.
"Capesaris DOES bind with with the PCa ERα activates it . That's EXACTLY how it works - it's a ERα agonist. That's exactly what an agonist means."
But the only paper I can find says:
"GTx-758 {Capesaris} reduced free testosterone and PSA earlier and to a greater degree than leuprolide."
A PSA reduction implies that the significant action is the more effective reduction if free T (which, of course, is not produced by PCa cells, let alone via the estrogen receptor).
"A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%)."
So without T, ER alpha is irrelevant as the AR cannot be activated anyway. Makes perfect sense. How about someone on active surveillance? Should ER alpha be activated or blocked in order to slow progression? If blocking it is desirable, then ursolic acid would be a handy tool to implement.
ERalpha is largely absent from normal epithelial cells. It replaces ERbeta as PCa develops.
Also, there is often heightened levels of aromatase in PCa cells. One might ask why the cancer wants to convert T to estradiol [E2].
I do believe that when not on ADT, ERalpha is a reasonable target.
One thing that can be done is to take the aromatase inhibitor Arimidex.
A more controversial step would be to correct T levels. ERalpha promotes growth. With low T, AR becomes growth-permissive. With normal T, AR assumes its regulatory role. We know that the prognosis is worse for men with low T. That should be addressed while on active surveillance.
Published online 2015 Oct 31. doi: 10.18632/oncotarget.6317
PMCID: PMC4792564
PMID: 26575018
Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer
Prostate cancer cells express ERα and are estrogen responsive
The effects of estrogen are mediated by the intracellular estrogen receptors (ERs), which regulate transcription through binding to specific DNA sequences called EREs (estrogen response elements) in the promoter regions of their target genes. When we checked the ERα, ERβ and AR status in different prostate cancer cells as well as in a benign prostatic hyperplasia cell line (BPH-1), we detected ERα protein in some prostate cancer cells and ERβ protein in all cell lines even though ERα mRNA was detected in all the cells tested.
Estrogen increases prostate cancer cell growth
To check the effect of estrogen on cell growth, we treated PacMetUT1 with estrogen and two different ER antagonists, tamoxifen and ICI 182,780 (ICI) respectively. Estrogen significantly increased the cell growth after 5 days of treatment. Both tamoxifen and ICI decreased the cell growth, which was reversed by the addition of estrogen suggesting the functional involvement of ERs in the regulation of PacMetUT1 cell growth. Furthermore, using an ERα specific antagonist, MPP also reduced the cell growth that was regained by the addition of estrogen.
Estrogens have been considered to be significant risk factors in the development of benign prostatic hyperplasia and prostate cancer. The presence of estrogen receptors in the prostate tissue suggests that estrogens can have functional roles in the prostate. It has been widely reported that ERβ is the predominant subtype, expressed in the majority of prostate epithelial cells, whereas ERα is expressed typically in the prostate stromal cells. ERα-positive cells have also been found in the hyperplastic epithelium of the prostatic ducts, but its functional role remains undefined.
In summary, our study revealed a novel role of estrogen signaling in promoting osteoblastic tumor formation in human prostate cancer cell lines. This oncogenic role of estrogen is mediated by ERα. Thus, inhibition of ERα signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development in patients with advanced stage prostate cancer.
Estrogen is beneficial for the treatment of prostate cancer because it activates the estrogen alpha receptor. This was demonstrated with Capesaris in humans. In mice, the activation of the estrogen alpha receptor inhibited prostate cancer, but activation of the estrogen beta receptor encouraged prostate cancer to grow:
It is MUCH more complex than this because there are a number of different alpha and beta receptors, each of which is expressed in different prostate cancers and which may have opposite effects.
Inositol (like all the B vitamins) is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe - there is no need to supplement it if you're eating normally. Just a way supplement manufacturers make money.
It wasn't about good and bad estrogens. They found that estrogen was METABOLIZED in a different way in men with prostate cancer vs men without prostate cancer. Their hope was to find a new biomarker (just as PSA is a biomarker) for prostate cancer. Here's the published study:
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
