Melatonin & AR-V7

New study below.

AR-V7 [Androgen Receptor Splice Variant-7] is an Androgen Receptor [AR] mutation that is common in CRPC [castration resistant PCa]. AR-V7 does not need androgen to become active.

"Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis."

"Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin."

I take 50 mg before bed.

...

"It is worth noting that melatonin, which acts by inhibiting both activated AR and NF-κB signaling in prostate cancer cells, has been demonstrated to be a novel prostate growth inhibitor]. Given that constitutively active androgen receptor splice variants, in particular AR-V7, have been shown to confer resistance to abiraterone or enzalutamide, and that activation of NF-κB and reactivation of AR signaling are involved in prostate cancer progression and CRPC development, it would be of interest to investigate any interactions among AR-V7, NF-κB, and melatonin in prostate cancer cells to gain further insights on the therapeutic potential of melatonin in advanced prostate cancer and CRPC management."

-Patrick

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

FULL Text: mdpi.com/1422-0067/18/6/113...

Int J Mol Sci. 2017 May 31;18(6). pii: E1130. doi: 10.3390/ijms18061130.

Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy.

Liu VWSWS1, Yau WL2, Tam CW3, Yao KM4, Shiu SYWYW5.

Author information

Abstract

A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.

KEYWORDS:

androgen receptor splice variant-7; castration-resistant prostate cancer; melatonin; nuclear factor-kappa B

PMID: 28561752 DOI: 10.3390/ijms18061130

12 Replies

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  • I tried to get through the paper, which is dense, as usual. However the only reference to dosage I could find was "the cells were treated with 10−6 M melatonin". What does this translate into something we can use, i.e., a therapeutic dose?

  • I doubt that one could extrapolate from a cell study.

    I use 50mg because LEF upped their recommendation from 40 to 50mg some years ago. Human melatonin studies start at 20mg, as I recall. I wouldn't go below 20 mg.

    -Patrick

  • Hi Patrick,

    I was wondering how you chose 50 mg the last time you mentioned it. I'm at 30 mg. Are you using 5 10 mg pills or have you found something larger? Thanks.

    Neal

  • Early to bed, early to rise. Eat your leafy greens. Exercise. Reduce stress.

    A good, natural start, perhaps.

  • Very,very interesting.

    Taking melatonin 10mg for sleep,placebo or not seems useful for me.

    How did you choose 50mg ?

    Any unwanted side effects ?

    Thanks

  • See my response to Neal, pasted below.

    I always sleep like a baby for the first 2 hours, so I would not have noticed an immediate sleep benefit. In fact, I don't understand those who liken melatonin to a sleeping pill.

    At the other end of the night, I wake refeshed befor 6 am. No grogginess. Again, I don't understand those who say that a high dose might leave one sleepy. Melatonin is an endocrine hormone without a feedback mechanism. Consequently, there is a local response where the receptors become increasingly resistant to it. &, of course, it is cleared long before the next night. So there should be no residual effects.

    On the other hand, melatonin can increase one's awareness of dreams. In some people (with chronic disturbing dreams), this can result in fitful sleep.

    -Patrick

    "Life Extension PCa protocol circa 2015 had 40 mg.

    LEF increased it to 50 mg at some point."

  • Fascinating, I take only 9-12mg time release melatonin. Can share who is your dr and whether he directed this or on your own?

  • When I started out 13+ years ago, there was little to go on but the Life Extension protocol.

    In time, I added a lot of things & dropped others. My integrative medicine doctor monitors what I use. He has made useful suggestions. Insurance doesn't pay, but he's worth it.

    I don't expect my GP & PCa docs to be up on otc products.

    -Patrick

  • I am a believer and a user.

    Nalakrats

  • Patrick,

    Have you taken the test for a AR-V7 mutation?

    Rich

  • Rich,

    No.

    -Patrick

  • Patrick,

    Thank you for both replys, including the one on Lupron Monotherpy. I am also taking 50 mg. of Casodex. I plan on going another 7 or 10 years.

    Rich

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