A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models.

[pjoshea13]

New study below.

The novel composition has 3 familiar components: luteolin, quercetin, and kaempferol.

"The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa in preclinical models. The three ingredients of ProFine demonstrated synergistic in vitro cytotoxicity and effectively induced apoptosis in PCa cells. ProFine markedly affected the transcriptome of PCa cells, suppressed the expression of androgen receptor, and inhibited androgen-regulated genes. Oral administration of ProFine did not exhibit obvious toxicities in mice, and the three ingredients retained their individual pharmacokinetic and bioavailability profiles. Importantly, ProFine significantly retarded the growth of PCa xenografts in athymic nude mice and extended the survival of animals. This study provides preclinical evidence supporting the promise of ProFine as a safe, efficacious, and affordable intervention to control PCa progression and improve clinical outcomes."

-Patrick

ncbi.nlm.nih.gov/pubmed/299...

Neoplasia. 2018 Jul 4;20(8):789-799. doi: 10.1016/j.neo.2018.06.003. [Epub ahead of print]

A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models.

Mamouni K1, Zhang S2, Li X1, Chen Y1, Yang Y1, Kim J3, Bartlett MG3, Coleman IM4, Nelson PS4, Kucuk O5, Wu D6.

Author information

1

Molecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.

2

Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.

3

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA.

4

Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.

5

Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.

6

Molecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA; Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; MetCure Therapeutics LLC, Atlanta, GA, USA. Electronic address: [e-mail].

PMID: 29981500 DOI: 10.1016/j.neo.2018.06.003

[cesanon]

"We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, "

Hmm seems interesting.

[snoraste]

One of my concerns about any chemicals that interferes with AR one way or the other is its interaction with other AR targeting agents (ADT/Zytiga/etc..).

[pjoshea13 in reply to snoraste]

In the case of ADT, & also of Zytiga, we are simply trying to starve the AR of its natural ligand. i.e. those therapies to not act directly on the AR. Antiandrogens such as Zytiga to act directly on the AR, by competing with natural ligands. Antiandrogens, however, do not activate the AR.

ProFine "suppressed the expression of androgen receptor". A response to ADT is often increased AR expression (more copies of the AR). Seems to me that there would not be conflict with standard treatments.

-Patrick

[podsart in reply to pjoshea13]

There might be problem with Xtandi as ,I believe it acts on the AR (signaling?)

[PhilipSZacarias]

Thank you for posting - a very useful paper. In response to comments by other members of this forum, Enzalutamide (Xtandi) is an androgen receptor (AR) antagonist, AR translocation inhibitor, AR DNA binding inhibitor and AR signaling inhibitor. Apalutamide (Erleada) is similar except it does not affect AR signaling (according to available info). DIM (diindolylmethane) is similar to enzalutamide in effects (and I am presently taking). The composition described in Patrick's post inhibits the expression of AR, which would appear to further hamper the ability of PCa cells to survive. I will read the paper and may comment later. Cheers, Phil

[Hidden]

I think they picked an odd name 'ProFine'. I googled it and found all kinds of hits. Herbicide, soy protein concentrate, company names. WTH. Was curious if it is available as a supplement.

[Hidden]

I think they picked an odd name 'ProFine'. I googled it and found all kinds of hits. Herbicide, soy protein concentrate, company names. WTH. Was curious if it is available as a supplement.

[smroush]

Interesting article. FYI, it looks like one or more of the authors is associated with the company MetCure which markets, or is planning to market, the ProFine supplement. The ProFine supplement is actually listed on Amazon, but with a stock status of currently unavailable.

I did a little bit of research on availability of luteolin, quercetin and kaempferol in foods and came up with these:

Luteolin - oregano (especially dried Mexican oregano), celery (esp. celery seeds), fresh thyme, fresh sage, dried parsley, green peppers, radicchio, and chamomile tea

Quercetin - capers, arugula, apples, red onions, radicchio, elderberry juice, red raspberries, blueberries, blackberries, dark cherries, grapes, broccoli, peppers, black tea, green tea, red wine, cruciferous veggies, spinach, kale

Kaempferol - Capers, Cumin, Cloves, Caraway, Kale, Fresh dill, Chives, Apples, Pepper, Red wine, Dark cherries and berries (blueberries, bilberries, blackberries and others), Tomatoes, Cruciferous veggies, including broccoli, cabbage and sprouts, Leafy green veggies, including spinach, kale, Citrus fruits.

Also, the US Department of Agriculture has a very useful document listing the flavonoid content of many foods and spices. The document can be found here:

ars.usda.gov/ARSUserFiles/8...