Enzalutamide resistance & IKKB - Advanced Prostate...

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Enzalutamide resistance & IKKB

pjoshea13 profile image
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New study below [1].

"Although enzalutamide (ENZ) has been widely used to treat de novo or castration-resistant metastatic prostate cancer, resistance develops, and disease progression is ultimately inevitable.

"There are currently no approved targeted drugs to specifically delay or overcome ENZ-resistance."

"... IKKB inhibitors suppressed the development of ENZ resistance in xenografts ..."

"IKKB upregulation appears to have greater relevance to the progression of human castrate resistant prostate cancer."

So we need to either inhibit IKKB upregulation or or inhibit IKKB activities.

IKKB [IKK-β] is the inhibitor of nuclear factor kappa-B kinase subunit beta. It causes activation of NF-κB (nuclear factor kappa-B). NF-κB is responsible for cell survival. As such it causes the transcription of scores of survival proteins.

NF-κB is the target of the polyphenols we commonly take for PCa.

[2] "Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells"

"... the anticancer properties of lycopene may occur through inhibition of the NF-κB signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-κB-responsive gene regulation."

[3] "Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation"

"... metformin prevented the translocation of NF-κB to the nucleus and inhibited the phosphorylation of IκB and IKKα/β, events required for activation of the NF-κB pathway."

[4] "Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo"

"Here we show that the natural compounds acetyl-beta-boswellic acid and acetyl-11-keto-beta-boswellic acid (AKbetaBA) inhibit proliferation and elicit cell death in chemoresistant androgen-independent PC-3 prostate cancer cells in vitro and in vivo. Induction of apoptosis was demonstrated in cultured PC-3 cells by several parameters including mitochondrial cytochrome c release and DNA fragmentation. At the molecular level these compounds inhibit constitutively activated NF-kappaB signaling by intercepting the IkappaB kinase (IKK) activity"

[5] "Therapeutic potential of curcumin in prostate cancer--V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells"

"The IKK activity was severely impaired, showing marked NF-kappa B inhibition."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/335...

[2] pubmed.ncbi.nlm.nih.gov/267...

[3] pubmed.ncbi.nlm.nih.gov/235...

[4] pubmed.ncbi.nlm.nih.gov/155...

[5] pubmed.ncbi.nlm.nih.gov/151...

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MateoBeach profile image
MateoBeach

Most excellent research Patrick. I will digest these all. Thank you. Of course you know about Niclosamide and bicalutamide for enzalutamide resistance:

ncbi.nlm.nih.gov/pmc/articl...

pjoshea13 profile image
pjoshea13

Hi Nal,

Nice day here in the mountains today - but cool.

I sometimes wonder what Denmeade is working on & why progress on BAT is so slow. Anyway, here's the list:

clinicaltrials.gov/ct2/resu...

MateoBeach profile image
MateoBeach

Wondering if us "early adapters" feel may be beneficial dosing for these interventions. Auch as: Is daily tomato or sauce intake sufficient for Lycopene? What does of Metformin for non-diabetics? Is 1000 mg/day enough? Adding reservatrol or pterostilbene? Is Boswellia serrata extract worth adding additionally? Curcumin seems a given at this point. Thanks Patrick

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