Inhibition of NFκB Reduces Prostate Cancer Related Osteoclastogenesis In Vitro and Osteolysis Ex Vivo.

[pjoshea13]

New UK study below [1].

See a post from 3 years back [2]:

"Foods/Supplements-Vitamins: Parthenolide - Feverfew"

I have also posted on inflammation & the role of chronically activated nuclear factor-kappaB [NFkB] in PCa. All the polyphenolic usual suspects are NFkB inhibitors.

In the new study, the target was NFkB because "NFκB is implicated in cancer and bone remodelling". The natural agent used was not a polyphenol, but a terpenoid (a sesquiterpene lactone) from the feverfew plant: Parthenolide [PTN].

If using a feverfew product, look for one where the Parthenolide content is shown, e.g. [3]: "(min. 0.5%-0.7% Parthenolide)"

RANKL [Receptor activator of nuclear factor kappa-Β ligand] "stimulated osteoclast formation and PTN reduced these effects without affecting prostate cancer cell viability".

{Note that Denosumab [Xgeva] is also a RANKL inhibitor.}

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/309...

[2] healthunlocked.com/advanced...

Calcif Tissue Int. 2019 Mar 30. doi: 10.1007/s00223-019-00538-9. [Epub ahead of print]

Pharmacological Inhibition of NFκB Reduces Prostate Cancer Related Osteoclastogenesis In Vitro and Osteolysis Ex Vivo.

Marino S1,2, Bishop RT1, Carrasco G1, Logan JG2, Li B1, Idris AI3,4.

Author information

1

Department of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.

2

Bone and Cancer Group, Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XR, UK.

3

Department of Oncology and Metabolism, Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. [e-mail].

4

Bone and Cancer Group, Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XR, UK. [e-mail].

Abstract

NFκB is implicated in cancer and bone remodelling, and we have recently reported that the verified NFκB inhibitor Parthenolide (PTN) reduced osteolysis and skeletal tumour growth in models of metastatic breast cancer. Here, we took advantage of in vitro and ex vivo bone cell and organ cultures to study the effects of PTN on the ability of prostate cancer cells and their derived factors to regulate bone cell activity and osteolysis. PTN inhibited the in vitro growth of a panel of human, mouse and rat prostate cancer cells in a concentration-dependent manner with a varying degree of potency. In prostate cancer cell-osteoclast co-cultures, the rat Mat-Ly-Lu, but not human PC3 or mouse RM1-BT, enhanced RANKL stimulated osteoclast formation and PTN reduced these effects without affecting prostate cancer cell viability. In the absence of cancer cells, PTN reduced the support of Mat-Ly-Lu conditioned medium for the adhesion and spreading of osteoclast precursors, and survival of mature osteoclasts. Pre-exposure of osteoblasts to PTN prior to the addition of conditioned medium from Mat-Ly-Lu cells suppressed their ability to support the formation of osteoclasts by inhibition of RANKL/OPG ratio. PTN enhanced the ability of Mat-Ly-Lu derived factors to increase calvarial osteoblast differentiation and growth. Ex vivo, PTN enhanced bone volume in calvaria organ-Mat-Ly-Lu cell co-culture, without affecting Mat-Ly-Lu viability or apoptosis. Mechanistic studies in osteoclasts and osteoblasts confirmed that PTN inhibit NFκB activation related to derived factors from Mat-Ly-Lu cells. Collectively, these findings suggest that pharmacological inhibition of the skeletal NFκB signalling pathway reduces prostate cancer related osteolysis, but further studies in the therapeutic implications of NFκB inhibition in cells of the osteoblastic lineage are needed.

KEYWORDS:

Bone; NFκB; Osteoclast; Osteoclastogenesis; Osteolysis; Prostate cancer

PMID: 30929064 DOI: 10.1007/s00223-019-00538-9

***

[3] iherb.com/pr/Now-Foods-Feve...

[Kuanyin]

Many years ago I looked into the possibility of using feverfew (parthenolide). Parthenolide stimulates oxidative stress. This stress inhibits JAK1 Kinase activity which results in the inhibition of STAT3 activation. Supposedly parthenolide reduces oxidative stress by reducing glutathione which, in turn, leads to a build up of ROS. It doesn't take much parthenolide to accomplish this, but the Joker is that parthenolide is almost completely insoluble in water. What I recall reading was the recommendation to dissolve the supplement in a mixture of 1/2 warm water and 1/2 cream before ingestion. The reason I never used feverfew was that, at the time, there weren't any parthenolide supplements. It would have required of me to buy 2-3 pounds of feverfew and decoct it to get the therapeutic amount and this would have had to be done daily: a laborious and time-consuming task. Now all of the work has been done for us.

[j-o-h-n in reply to Kuanyin]

Stupid me... Am I sorry now....I decided to take up basket weaving instead of Latin.

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 04/02/2019 7:14 PM DST

[j-o-h-n]

Stupid me... Am I sorry now....I decided to take up basket weaving instead of Latin.

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 04/02/2019 7:13 PM DST