NF-κB Signaling Promotes Castration-Resistant Prostate Cancer Initiation and Progression

[pjoshea13]

New paper below, [1].

The PCa literature was pretty clear about the role of NF-kB [Nuclear Factor-kappaB] even 16 years ago. This was the beginning of my interest in phyto-polyphenols. While they are all antioxidants (pro-oxidant at pharma-levels), they also inhibit NF-kB.

Under normal circumstances, NF-kB is tied to a protein that prevents it moving to the nucleus of the cell. If a cell experiences viral or bacterial insult, the protein will be unhooked & NF-kB will trot off to do its thing.

Once an organ has attained its full size in an adult, cells die & other cells divide over time, but the organ maintains its size in a healthy person. Under viral attack, cell death might outrun cell creation. The main purpose of NF-kB is to place a moratorium on cell death. All well & good during a COVID-19 attack, but PCa chronically activates NF-kB, allowing tumors to grow.

NF-kB is responsible for the LOX/COX enzymes that target arachidonic acid & create inflammatory metabolites. Useful during an infection, but detrimental for someone with cancer. But it does much else. Scores of proteins are trancribed that all have an effect on cell survival.

From the new paper:

"... NF-κB signaling is also implicated in the initiation and maintenance of CRPCa and, thus, the NF-κB pathway may be a promising alternative therapeutic target. In this review, we present evidence that NF-κB signaling promotes CRPCa initiation and progression, describe the dichotomic role of NF-κB in the regulation of AR expression and activity and outline studies that explore NF-κB inhibitors as PCa therapies."

NF-kB has always been my primary target. How do we know that NF-kB is under control? Monitor inflammatory markers sucha as albumin & C-Reactive Protein. I have a series of 4 posts on inflammation.

My resource for NF-kB info has been Tom Gilmore at Boston U. [2] [3] (Table 1: Antioxidants that have been shown to inhibit activation of NF-kB).

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/322...

Review Pharmacol Ther

, 107538 2020 Mar 19[Online ahead of print]

NF-κB Signaling Promotes Castration-Resistant Prostate Cancer Initiation and Progression

Shayna E Thomas-Jardin 1 , Haley Dahl 1 , Afshan F Nawas 1 , Monica Bautista 1 , Nikki A Delk 2

Affiliations collapse

Affiliations

1 Biological Sciences Department, The University of Texas at Dallas, 800 West Campbell Road, FO31, Richardson, TX 75080, United States of America.

2 Biological Sciences Department, The University of Texas at Dallas, 800 West Campbell Road, FO31, Richardson, TX 75080, United States of America. Electronic address: [e-mail].

PMID: 32201312 DOI: 10.1016/j.pharmthera.2020.107538

Abstract

Prostate Cancer (PCa) is the second leading cause of cancer-related death in men. Adenocarcinoma of the prostate is primarily composed of Androgen Receptor-positive (AR+) luminal cells that require AR transcriptional activity for survival and proliferation. As a consequence, androgen deprivation and anti-androgens are used to treat PCa patients whose disease progresses following attempted surgical or radiation interventions. Unfortunately, patients with advanced PCa can develop incurable castration-resistant PCa (CRPCa) due to mutated, variant, or overexpressed AR. Conversely, low or no AR accumulation or activity can also underlie castration resistance. Whether CRPCa is due to aberrant AR activity or AR independence, NF-κB signaling is also implicated in the initiation and maintenance of CRPCa and, thus, the NF-κB pathway may be a promising alternative therapeutic target. In this review, we present evidence that NF-κB signaling promotes CRPCa initiation and progression, describe the dichotomic role of NF-κB in the regulation of AR expression and activity and outline studies that explore NF-κB inhibitors as PCa therapies.

Keywords: Androgen receptor; Castration resistance; Nuclear factor-κB; Prostate Cancer.

Copyright © 2020. Published by Elsevier Inc.

***

[2] bu.edu/nf-kb/

[3] bu.edu/nf-kb/table-1/

[pjoshea13]

He probably does, but the site is pure info - no opinion. What I like is the link to known studies. I don't know when it was last updated.

-Patrick

[PhilipSZacarias]

Most interesting. I am taking several of these. I wonder which ones are the most efficacious? Thanks. Phil

[noahware]

"Table 1" is just a bit too extensive (at well over 100 items) to be helpful in practical terms, I fear, without having any idea of the degree to which any of these might be inhibitory. Any ideas, anyone?

[LearnAll in reply to noahware]

Common ones are: curcumin, quarcetin, grape seed extract, green tea extract, melatonin,

sulforaphanes and the list goes on...until your CRP goes below 0.4.

[Shanti1]

Great post! Thanks Patrick!

[Schwah]

I consider myself an educated Man. More than most I’m Sure but this is way over my head. For all us “dummies” out there who read that post, can you please give us a cliff note version of the practical implications in our own PC battles. It would be greatly appreciated.

Schwah

[TFBUNDY]

Hi Patrick. My C reactive protein was 7 last month. No-one seems excited by that except me. I have a very painful shoulder which I think is rotator cuff damage, which may be the cause. At the same test my PSA was up from around 1.2 to 1.8. This may be due to weekly self catheterization for dilation, although i had left it for 8 days before the blood test I am well aware of inflammation and NF kB but don't know what to do to knock it back. Does anyone have any ideas? At the moment I use Atorvastatin, LDN, vit D and low dose aspirin. Beginning ibruprofen + green tea extract. Cheers

[Shanti1 in reply to TFBUNDY]

There are two versions of the CRP test that docs run, one is a high sensitivity (hs) aka cardiac CRP and the other is regular CRP, the reference range is different for the two. For hs-CRP the range is typically <3 and for standard CRP normal is usually <10. Do you know which test you had done?

[Scout4answers]

Have you refined this list or figured out which ones would be most beneficial?

[pjoshea13 in reply to Scout4answers]

I suppose that my top 5 would be:

A] apigenin

C] curcumin

F] fisetin

Q] quercetin

R] resveratrol

[C] swansonvitamins.com/now-foo...

[F] & [R] I prefer the RevGenetics products. Expensive, but I wait for the 50% sale

-Patrick

[Scout4answers in reply to pjoshea13]

Thanks Patrick apigenin and fisetin are new to me. starting to read up on them.