Melatonin - AR-V7 Splice Variant.

[pjoshea13]

The study below [1] is a cell study from last year. I don't think it has been posted before.

As many here know, a common reason for resistance to Zytiga or Xtandi is selection for androgen receptor [AR] splice variant dominance, particularly for AR-V7.

AR-V7 is AR without the bit where the androgen binds (the C-terminal ligand binding domain). & yet it somehow remains functional & participates in cell division.

In the study, AR-V7 was seen to induce activation on NF-kB (Nuclear Factor-kappaB), & activated NF-kB in turn was able to induce AR-V7 expression. Melatonin inhibited NF-kB.

Frankly, it's rare for NF-kB to not be activated in serious PCa. All of the common polyphenols that I have written about are NF-kB inhibitors. NF-kB induces many cell survival proteins, including the pro-inflammatory COX/LOX enzymes. Inhibition of NF-kB is a must IMO.

"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."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[cesanon]

hmmmm, Patrick could you translate that? LOL

[pjoshea13 in reply to cesanon]

Melatonin might be useful in men on Zytiga or Xtandi, since it might inhibit resistance. -Patrick

[pjoshea13]

I take my 50 mg Melatonin before turning out the light. Along with my Simvastatin, Avodart, nattokinase, Iodoral Petadolex (for optical "migraines").

-Patrick

[Hidden]

Same here, definitely. Been on 3 mg for many years.

[cigafred]

I said the exact same thing to my MO at our last meeting. He said he thought that would not be a problem, but made no claims to knowledge.

[pjoshea13]

Cap size is small - see:

lifeextension.com/Vitamins-...

0.563"L x 0.209"W

There is a 20 mg product (not LEF), but it is $70 for 100 caps.

-Patrick

[pjoshea13]

Some people seem to believe (or are led to believe) that because melatonin is produced during sleep, it must be akin to a sleeping pill. That doesn't make sense to me, & it isn't my experience.

It is said that older people sometimes have a problem sleeping because older pineal glands tend to produce less melatonin. However, as anyone who has ever felt the need for a daytime nap knows, darkness & melatonin are not essential for sound sleep. Older people may well benefit from a melatonin supplement for other reasons, & a very small dose is all that is generally needed.

It's crazy for a healthy person to want to take more than the smallest dose. But for cancer, a pharmaceutical dose may have benefit. The prostate contains receptors for this hormone. Why? The research that I remember most is that melatonin can prevent the androgen receptor [AR] from relocating to the nucleus, & that AR that is already in the nucleus will be kicked out. I liked the idea that my cancer might not be in proliferation mode while I slept. Daytime is another problem.

-Patrick

[Bluebird11]

Nalakrats... we had a consult with a doc who specialized in PCa and also ozone therapy..

we dismissed the amount.. I swear it was double what Patrick takes though through suppository..

I need to look into this.. and if anyone finds any reference to this and suppository please let me know...

It can bypass the liver through suppository....

I know very little though I've been in this for a dozen years.. somehow age is creating cracks where information is escaping .. <smile> .. it's all okay...

[Bluebird11]

I know it would. This is why we didn't risk it.. but it was 100 ml...

we are going to up it.

we are going to do it slowly.

thanks for your comment, it is appreciated.

[Trecento]

Thanks for this post. My husband has just stopped taking Xtandi. But I’m assuming from you post and others’ that melatonin is a good idea regardless? Recently he has had to have opioid painkillers, any views on whether they should be taken simultaneously? Looked on drug interactions database but not terribly edifying.

[pjoshea13 in reply to Trecento]

I have taken melatonin almost every night for 15 years. At first, the 40 mg suggested by Life Extension [LEF], & then the 50 mg that LEF now recommends. The high dose isn't for improved sleep - it's specifically for cancer.

There is a possibility that melatonin & the opioid painkiller will work well together, but I can't find a study that proves it. Melatonin itself acts on opioid receptors & relieves pain. Which suggests to me that the painkiller should not be taken before bed with melatonin, unless necessary.

I doubt that many doctors would know the answer.

-Patrick

[Trecento in reply to pjoshea13]

Very helpful, thank you so much.