I was fortunate to come across a bunch of papers 17 years ago that identified Nuclear Factor-kappaB [NF-kB] as a potential target in PCa. I also discovered that countless natural polyphenols inhibit NF-kB. But for those who prefer drugs, there is Dimethylaminoparthenolide.
A new paper: "NF-κB blockade with oral administration of dimethylaminoparthenolide, delays prostate cancer resistance to androgen receptor inhibition and inhibits AR variants". [1]
There was another Dimethylaminoparthenolide / NF-kB paper in 2017: "DMAPT inhibits NF-κB activity and increases sensitivity of prostate cancer cells to X-rays in vitro and in tumor xenografts in vivo" [2].
I wrote about NF-kB 5 years agoin: "Cancer - Inflammation - Hypercoagulation - Metastasis" [3]
"Cancer is a chronic inflammatory state - this is due to NF-kB (nuclear factor-kappaB) activation.
"When we are under bacterial or viral attack, there is a danger that cell death (apoptosis) might outstrip cell division. NF-kB is activated to get us through the crisis. First there is a moratorium on cell death. Next there is the production of COX/LOX enzymes that act on arachidonic acid to trigger the production of inflammatory metabolites. A large number of other pro-survival proteins are also produced.
"NF-kB isn't supposed to be chronically activated, but that's what happens in cancer."
Here are some examples of natural substances and drugs which reduce systemic inflammation in body:
Turmaric, Ginger, Garlic,Cinnamon, Quercetin, Apigenin, EGCG (Green and Black tea), Resveratrol (Dark red grapes, Pink Guava, Peanuts) , Capsaicin (green and Red chilli)
Black long pepper, Black seed Oil. Boswellia Extract.
Meds: Ibuprofen (inhibits Cox1 and 2), Indomethacin (both Cox1 and 2), Diclofenac sod.(both cox1 and 2), Celecoxib (Cox2), Naproxyn (both Cox1 and2)
A combination of these can reduce C Reactive Proten ,a measure of Inflammation..significantly.
Last year I went through some NIH studies. They all agreed within a fairly tight range. Melatonin has dual antioxidant/pro-oxidant actions depending on the dose. I came up with:
"Anti-Cancer In High Doses >15mg, Antioxidant In Low Doses <3mg might reduce inflammatory cytokines (e.g. NF-κB). Some of these cytokines might be involved in ADT leading to CRPC."
The NF-kB is courtesy of the link you posted. Thanks.
"Though the pathogenesis of prostate cancer (PCa) is still obscure, it has been reported, by investigators previous studies and some other researches, that PCa is often combined with tissue inflammation which is closely related to prostate specific antigen (PSA) level. Inflammation could play an important role in the process of occurrence and development of PCa, however the mechanism is unknown. Inflammatory cytokines could not only mediate inflammatory reactions, but also participate in the growth, proliferation, invasion and progression of tumor cells. It has been found that non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin, can effectively prevent several inflammation related tumor, and coincidentally, PCa is also closely associated with inflammation. Moreover, latest researches demonstrated that hormone therapy could induce tissue inflammation in PCa, in which a large quantity of immune B cells were attracted into the focal and then a lot of cytokines, such as IKK-β, NF-κB, were released. These cytokines could inhibit apoptosis and promote the growth of tumor cells, which might be a possible mechanism for long-term inflammatory infiltration inducing the occurrence of PCa and the transformation to castration-resistant prostate cancer (CRPC)."
I think you've covered lots of this but two of the common things I take have a good amount of research and studies and might block cytokines like NF-kB: statins and metformin (edit: and melatonin)
I take 3600 mg a day of red yeast rice (supposedly more effective than a statin - works great to lower cholesterol): HPF Cholestene
1500 mg a day of metformin. My testing shows it does lower blood glucose. On a short-term basis exercise is better - so jump on a bike or take a walk after eating. Longer-term for metformin.
1 mg a day of melatonin (only at night). For one week a month, I take 100mg+ of melatonin at night. Dual antioxidant/pro-oxidant actions. Anti-Cancer In High Doses >15mg, Antioxidant In Low Doses <3mg.
I do not know how to compare these two,. I am taking TONIIQ brand high strength in which 1 cap contains 1000 mg Boswellia Extract. ( 85% Boswellic acid) . I have no side effects.
Thank you Patrick. My Advanced Prostate Cancer, PSA 1,311, was only diagnosed after a second DVT in my legs. This is the first writing I have seen on the subject of Coagulation and Thrombosis.
I am prescribed a anticoagulant, Apixaban (Eliquis). Due to the increase in risk of bleeding this causes, I am unable to take Aspirin. I am on quarterly Prostap ADT injections and Enzalutamide for the Metastasied cancer.
I have signed up to the Care Oncology Clinic and do take Metformin and Atorvastatin. In the UK we need a doctor to prescribe Melatonin, so I need to talk with my GP about this.
This is an area that really resonates but there do not appear to be clinical trials or drugs that hit the double wammy of cancer and recurrent thrombosis in synergy.
If anyone has any additional thoughts and suggestions, recommendations then do please advise.....
Once again, thank you Patrick. This information is really helpful and just not addressed enough from what I can see by the medical profession.
Hi, Patrick. I google this DMAPT. And i found that:Parthenolide is a sesquiterpene lactone found in Mexican-Indian medicinal plants such as Tanacetum parthenium. It has been widely used in indigenous medical practices for the treatment of migraine, inflammation and tumors.1-4 Parthenolide inhibits IkB kinase (IKK) and IKKβ (the upstream activators of the Nuclear Factor-kB (NF-kB) pathway), thus inhibiting Interleukin 1- and tumor necrosis factor a (TNFα) without affecting the activation of p38 and c-Jun N-terminal kinase.5,6
So do you think it is worth to add "Feverfew" to anti inflammators list?
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