Capsaicin

[pca2004]

A new U.S. study below [1].

I see that there are currently 48 PubMed hits for PCa/Capsaicin. Of interest recently:

[2] (2022, Spain) "The Natural Chemotherapeutic Capsaicin Activates AMPK ..."

[3] (2020, China) "Capsaicin suppressed activity of prostate cancer stem cells ..."

I use the 100,000 heat unit version from "Nature's Way", but it seems to have disappeared, so see: [4]. Absolutely no burning or irritation.

There are a slew of PCa papers on heat shock proteins [HSPs]. There was a useful paper last year: "Heat Shock Protein 70 and 90 Family in Prostate Cancer" [5] (full text).

From the Abstract:

"... The heat shock protein (HSP) family has cell-protective properties that may promote tumor growth and protect cancer cells from death. On a cellular level, HSP molecules have a strong relationship with multiple important biological processes, such as cell differentiation, epithelial–mesenchymal transition (EMT), and fibrosis. Because of the facilitation of HSP family molecules on tumorigenesis, a number of agents and inhibitors are being developed with potent antitumor effects whose target site is the critical structure of HSP molecules. Among all target molecules, HSP70 family and HSP90 are two groups that have been well studied, and therefore, the development of their inhibitors makes great progress. Only a small number of agents, however, have been clinically tested in recruited patients. ..."

From the new paper Abstract [1]:

"Heat shock protein 90 (Hsp90) and its co-chaperones promote cancer, and targeting Hsp90 holds promise for cancer treatment. Most of the efforts to harness this potential have focused on targeting the Hsp90 N-terminus ATP binding site. Although newer-generation inhibitors have shown improved efficacy in aggressive cancers, induction of the cellular heat shock response (HSR) by these inhibitors is thought to limit their clinical efficacy. Therefore, Hsp90 inhibitors with novel mechanisms of action and that do not trigger the HSR would be advantageous. Here, we investigated the mechanism by which capsaicin inhibits Hsp90. Through mutagenesis, chemical modifications, and proteomic studies, we show that capsaicin binds to the N-terminus of Hsp90 and inhibits its ATPase activity. Consequently, capsaicin and its analogs inhibit Hsp90 ATPase-dependent progesterone receptor reconstitution in vitro. Capsaicin did not induce the HSR, instead, it promoted the degradation of Hsp70 through the lysosome-autophagy pathway. ..."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/376...

[2] pubmed.ncbi.nlm.nih.gov/352...

[3] pubmed.ncbi.nlm.nih.gov/317...

[4] swansonvitamins.com/p/solar...

[5] ncbi.nlm.nih.gov/pmc/articl...

[GreenStreet]

Thanks very much for posting this Patrick. I did have a serious go at this a few years back working up to taking 6 x 100,000 HU from Natures Way. I did this alongside my other supplements for about 3 to 6 months from memory but I discontinued as it seemed to have no impact on my PSA doubling time. The cayenne was the extra supplement that I added on at the time. Again from memory it was a bit of a nuisance in that it needed to be consumed with food and I wanted to do 100,000 at a time and not double up to 200,000 lol. But we are all individual and it might help some. How many of the Natures Way did you take per day and did you ever double up to 200,000 at a given meal. I think they may sell the lesser 40,000 unit version still.

[pca2004 in reply to GreenStreet]

At 100,000 HU, I never felt the need to double-up - let alone take 6!

Yes, the 40,000 is still out there.

-Patrick

[GreenStreet in reply to pca2004]

Lol. I think Snuffy Myers once did a video on it and it seemed that a high dosage or the more risky consumption of very hot peppers had helped a couple of individuals. Did not do for me unfortunately but at the time seemed to be worth a controlled punt but I took care to build up slowly

[cujoe]

Patrick, I jumped into heat shock proteins several months back and it seemed a bit like a Looking Glass Darkly topic. My understanding is that they are "chaperones" for misfolded proteins and can, therefore, be helpful or detrimental. My concern originated out of regular sauna use which would surely foster some increase in heat-shock proteins. (Which ones??) With the other benefits of sauna use, I was trying to decipher if it might actually be bad for those of us with PCa? After endless searches to connect the dots, I basically came up empty-handed, and with no definitive resolution, am continuing with regular saunas and steams at the local Y.

BTW, I've been taking a Cayenne supplement and using it in spice form daily for many years now. I used NW until recently. My current one is 24k HU and I never considered the super-high dosage that GreenSt tried.

Some like Hot! Stay Well,

Ciao - Capt'n cujoe

[pca2004 in reply to cujoe]

Cujoe,

When my RP turned out to be ineffective, I was reading on how heat might be used to kill cancer cells.

My biology teacher at school told us that the testicles had to be outside the body because sperm cells had to be kept cool. Pure nonsense. However, testicular cancer cells that migrate into the body are at a disadvantage because of the higher temperature. Metastases are easier to treat, apparently.

So it seemed like maybe a good idea to sit in hot water to stress-out localized PCa cells. Until I read about heat shock proteins.

Turns out that there is nothing one can do to PCa cells without causing existing cell survival mechanisms to kick-in. Which is why I am not in favor of using aggressive palliative treatments. If you can't kill it, you will make it stronger.

-Patrick

[PCaWarrior]

If you are using BAT or another high testosterone therapy messing with the HSPs might not be advisable. Maybe it would be good. Maybe it should only be done during low T and maybe it should be stopped well before high T to allow HSP regeneration? I have tried to figure it out but haven't found enough conclusive data. Are HSPs needed for dimerization? Or are they a coincidental tag along? What about intracellular AR activation? Perhaps HSPs could be manipulated at certain times to turn BAT into a 3-phase approach. But when and how?

And I have also tried to find data on saunas and HSPs. I haven't unearthed anything.

"The primary mechanism of action for androgen receptors is direct regulation of gene transcription. The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene transcription.[20] Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is the insulin-like growth factor 1 receptor (IGF-1R).[21] Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior."

[Kuanyin]

Many years ago, I would take a Habanero pepper, cut it into piece and place it on a slice of buttered bread. I did this for at least a couple of years, then I stopped after I read of incidence of stomach cancer linked to hot peppers.

[pca2004 in reply to Kuanyin]

And yet:

"Capsaicin-induced cell death in a human gastric adenocarcinoma cell line"

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

-Patrick

[Kuanyin in reply to pca2004]

Yeah, I know. Search long enough and one can find a study to support a position. What I recall is finding conflicting studies. I just decided that I didn't want to deal with two serious forms of cancer. If you feel that it's worth the candle go ahead. I am already using myself as a guinea pig in other areas.