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: nikki.delk@utdallas.edu.
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/
Long term AR signaling‐targeted therapy with taxane sometimes associated with visceral metastasis in castration‐resistant prostate cancer
