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Androgens (DHT, T) Treat Prostate Cancer, Especially When Combined With Vitamin D

Discussion in 'Scientific Studies' started by haidut, Sep 2, 2016.

  1. haidut

    haidut Member

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    I recently posted a study showing that vitamin D inhibits the deactivation of androgens, which results in a build up of strong androgens like DHT.
    https://raypeatforum.com/community/threads/vitamin-d-inhibits-the-deactivation-of-androgens.12411/
    That study conclude that this effect of vitamin D is worrisome as it may lead to prostate cancer progression. However, in vivo studies have repeatedly shown that vitamin D is protective against prostate cancer and a few animals trials suggested that it may even treat the condition when used in high doses. If vitamin D increases androgen levels and is also therapeutic for prostate cancer, it is would not be a fat fetched conjecture that maybe androgens are also therapeutic for prostate cancer, contrary to the official dogma of the "evil DHT". And of course, this is what the evidence points to. Following are a few studied of unrelated researchers that all found androgens, alone or in combination with vitamin D, to be therapeutic for prostate cancer. The especially damning evidence against the androgen theory of prostate cancer is found in studied #2 and #4 below, which used specifically DHT (along or in combination with vitamin D) and found it to be highly therapeutic for prostate cancer.


    1,25-Dihydroxyvitamin D3 modulates lipid metabolism in prostate cancer cells through miRNA mediated regulation of PPARA. - PubMed - NCBI
    "...Previous studies from our laboratory have shown that testosterone (T) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) co-operate to inhibit cell proliferation and induce significant changes in gene expression and differentiation in LNCaP cells. The data presented here demonstrate that the two agents alter fatty acid metabolism, and accumulation of neutral lipid. Concurrent genome wide analysis of mRNA and miRNA in LNCaP cells reveals an extensive transcription regulatory network modulated by T and 1,25(OH)2D3. This involves not only androgen receptor (AR)- and vitamin D receptor (VDR)-mediated transcription, but also transcription factors E2F1- and c-Myc-dependent transcription. Changes in the activities of these transcription factors alter the steady state levels of several miRNAs, including the miR-17/92 cluster. These changes correlate with the up-regulation of the mRNA encoding peroxisome proliferator-activated receptor alpha (PPARA) and its downstream targets, leading to increased lipogenesis. These data suggest that the coordinated effect of T and 1,25(OH)2D3 in prostate cancer cells increases lipogenesis, diverting energy away from Warburg-based tumor energy metabolism, which slows or halts cell growth and tumor progression."

    "...In this context, the cancer preventive property of vitamin D3 in prostate cancer can be partly attributed to the effects on miR- 17/92 cluster and the subsequent PPARA expression. The ability of 1,25(OH)2D3 to slow disease progression is also augmented by androgen action in androgen responsive PCa. These findings offer a mechanistic explanation for the epidemiological data linking T and vitamin D3, and suggest that maintenance of serum T and critically, vitamin D3 levels in older men may be sufficient to render many prostate cancer cases indolent."


    1. The role of insulin-like growth factor binding protein-3 in the growth inhibitory actions of androgens in LNCaP human prostate cancer cells. - PubMed - NCBI
    "...In the present study, we treated LNCaP cells with various concentrations of the synthetic androgen R1881 alone or in combination with calcitriol and studied their effects on IGFBP-3 expression and cell proliferation. For the first time we show that IGFBP-3 is involved in mediating the antiproliferative effects of high concentrations of R1881 at least in part through stimulation of the p21/p27 pathway. Our findings provide new insights into the mechanisms by which androgens cause a biphasic growth response in LNCaP cells.

    "...To determine whether androgen induction of IGFBP-3 correlates with this biphasic growth phenomenon, we treated LNCaP cells with increasing concentrations of R1881 (0–100 nM) and examined cell growth and induction of IGFBP-3 protein expression. As shown in Figure 4a, 0.1 nM R1881 stimulated cell growth but did not change IGFBP-3 protein level relative to the control. In contrast, concentrations equal to or higher than 0.5 nM R1881 increased IGFBP-3 protein ∼3-fold, while reducing cell proliferation ∼48% compared with the control. Higher concentrations of R1881 further increased IGFBP-3 and reduced growth. Furthermore, treatment with 10 nM of R1881 and calcitriol together produced a synergistic increase of IGFBP-3 expression (Fig. 4b) and also resulted in a greater cell growth inhibition. The data suggest that induction of IGFBP-3 is correlated with androgen-induced growth inhibition in LNCaP cells."


    2. Androgen enhances the antiproliferative activity of vitamin D3 by suppressing 24-hydroxylase expression in LNCaP cells. - PubMed - NCBI
    "...25-Hydroxyvitamin D3-24-hydroxylase (24-hydroxylase, CYP24) is an important inactivating enzyme controlling the concentrations of both active metabolites 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3. In this paper, we demonstrate that 25-hydroxyvitamin D3 at 500 nM significantly increases the expression of 24-hydroxylase mRNA and the increase is significantly decreased by 5alpha-dihydrotestosterone (DHT) at concentrations of 1-100 nM in androgen-sensitive prostate cancer cells LNCaP. 25-Hydroxyvitamin D3 at 500 nM and 1alpha,25-dihydroxyvitamin D3 at 10 nM inhibit LNCaP cell growth, and the growth inhibition is enhanced by 1 nM DHT. Neither 25-hydroxyvitamin D3 nor 1alpha,25-dihydroxyvitamin D3 at physiological concentrations has growth effect. However, in the presence of 1 nM DHT, both 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 at physiological concentrations are clearly antiproliferative. These data demonstrate that DHT enhances the antiproliferative activity of Vitamin D3 hormones by inhibiting their inactivating enzyme. Most previous studies on Vitamin D3 action in cell cultures have used pharmacological concentrations of 1alpha,25-dihydroxyvitamin D3, the present results demonstrate, for the first time, that both 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 at physiological concentrations are active in the presence of physiological concentration of androgen. The combined use of androgen and Vitamin D3 metabolites could be a promising treatment for prostate cancer."


    3. Vitamin D and androgen regulation of prostatic growth. - PubMed - NCBI
    "...Vitamin D has been reported to inhibit the growth of prostate cancer cells and model systems. In this study, we examined the interaction between 1,25-dihydroxyvitamin D(3) (1,25 D) in the presence or absence of endogenous testosterone on the growth and development of the adult rat prostate. Male Sprague-Dawley rats (165 days old) were either kept intact or castrated. Seven days after castration, the rats were treated with vehicle (control) or 1,25 D for 3 weeks and then sacrificed. Both ventral and dorsal lateral prostates were harvested; whole tissue lysates were collected and AR and VDR protein levels were analyzed by immunoblot analyses. Administration of 1,25 D in the intact animals decreased the prostatic size by 40%, compared to control animals, whereas 1,25 D did not influence the size of the prostate in castrated rats. 1,25 D administration in intact groups also increased both the AR and VDR protein levels by approximately twofold, whereas in castrated groups, 1,25 D only increased the AR protein level by 1.5-2.5-fold. 1,25 D in the presence of endogenous testosterone inhibits prostatic growth, whereas 1,25 D in the absence of endogenous testosterone does not affect prostatic growth. The growth inhibitory activity of 1,25 D in the presence of testosterone may be mediated through the ligand activated AR and VDR pathways. These studies may reveal important information about the potential efficacy of 1,25 D as well as hormonal status in understanding the development of prostate diseases."


    4. 1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent. - PubMed - NCBI
    "...We and others have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible interactions between 1,25-(OH)2D3 and androgens in the regulation of LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25-(OH)2D3 (60% inhibition at 10 nM) when cells were cultured in medium supplemented with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA secretion 22-fold. This synergistic effect was even greater when cells were cultured in medium supplemented with charcoal-stripped serum (CSS medium), where endogenous steroids are substantially depleted. Under these conditions, 1,25-(OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the untreated control. Radioligand binding assays and Western blot analyses showed that the androgen receptor (AR) content was increased significantly by 1,25-(OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA secretion. Titration experiments revealed that the addition of DHT at 1 nM to the medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA stimulation activities when cells were cultured in FBS medium. In conclusion, these results demonstrate that the antiproliferative and PSA induction activities of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up-regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25-(OH)2D3 and DHT in these cells."
     
  2. OP
    haidut

    haidut Member

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    Hhhmm, for some reason this post of mine shows as "thread" while all the others I made recently show as "post". Is this normal @charlie ? Maybe it's because this post has no comments yet...
     
  3. charlie

    charlie The Law & Order Admin

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    @haidut, everything seems OK. Or am I missing something? :confused2
     
  4. milk_lover

    milk_lover Member

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    Thanks haidut for all the information you give us on a daily basis. It has helped me and many of my family :) Is it a myth I have to take K2 with D3? I never saw Ray mention that condition. Also, when I took D3 with DHEA yesterday, per your advice in the other thread, I get a glowing and smooth face and overall happy mood.
     
  5. OP
    haidut

    haidut Member

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    I guess everything is fine in terms of workings. I just noticed that one of the posts under "My content" was showing up as "Thread" while all others were of type "post" and when I clicked on the "thread" post it popped up a message "invalid thread" or something like that. I guess it is all working now.
     
  6. charlie

    charlie The Law & Order Admin

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    Oooh, you had double posted a thread yesterday so I soft deleted one of them. Once I hard delete it, it wont show up in your search.
     
  7. OP
    haidut

    haidut Member

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    You can take K2 on its own, there is no need to take with D3. It's just that if you take with D3, it will help put the absorbed calcium into the bones and not the soft tissues.
     
  8. OP
    haidut

    haidut Member

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    Got it, thanks.
     
  9. Jsaute21

    Jsaute21 Member

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    @haidut im new to the forum but would you mind outlining your dietary strategy throughout the day?
     
  10. OP
    haidut

    haidut Member

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    Please ask this in another thread, this thread is for androgens and prostate cancer. And before you start a new thread, please search the forum. I must have had this question asked 20 times and have answered it just as many times. The diet changes (like everything else in this Universe), but some general principles remain.
     
  11. Blossom

    Blossom Moderator

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  12. gilson dantas

    gilson dantas Member

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    yes, I´m reading it, thanks @Blossom.
     
  13. SQu

    SQu Member

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    One of many things I've got my dad doing that may be contributing to his prostate improvement is getting noonday sun for the vit d.

    His doc prescribed firmagon injections and avodart after saying dad did not need any further treatment - then when queried on them, immediately said no need to take. Pretty certain he just reflexively prescribes for all such patients even having said himself they're not needed in this case. No doubt seeing dozens of patients a day he forgets these details.

    @Blossom or @charlie, I have a conversation with @haidut about my dad's prostate issues that haidut thinks could help others. How to move it to a thread?
     
  14. sladerunner69

    sladerunner69 Member

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    So the dosages in these studies appear to be the human equivalent of 10k-50k each day correct? That is a load of vitamin d caps. Does the source matter much? I take cholocalciferol vitamin D 10000iu with vitamin A 10000iu twice a day. I think it helps me feel more energetic due to an increase in androgenic activity, which is my primary health concern-low androgenic activity.
     
  15. Blossom

    Blossom Moderator

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    You can start a new thread and copy and paste the conversation to the text box.
     
  16. SQu

    SQu Member

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    Thanks blossom, I just did that.
     
  17. Blossom

    Blossom Moderator

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