Perillyl alcohol inhibits androgen receptor function and expression

Topicals for hair loss
1

Titre du document / Document title
Perillyl alcohol inhibits the expression and function of the androgen receptor in human prostate cancer cells
Auteur(s) / Author(s)
BYUNG HA CHUNG ; LEE Hye-Young ; JAE SEOK LEE ; YOUNG Charles Y. F. ;
Résumé / Abstract
Perillyl alcohol is a hydroxylated monocyclic monoterpene. In animal study, monoterpene has shown to have an anti-tumor effect. The aim of this study is to evaluate whether POH plays an important role in the development and progression of prostate cancer (pCa). We treated LNCaP cells with different concentrations of perillyl alcohol (POH). First of all, we performed cell proliferation assay and prostate-specific antigen (PSA) and human glandular kallikrein (hK2) quantification assays. LNCaP cells were treated with or without POH for Western blot analysis of androgen receptor (AR) and c-Jun. Finally, we performed transient transfection assay by transfecting LNCaP cells-which were treated with or without POH-with pGL-3 luciferase vector containing PSA promoter and AR promoter. We observed inhibition of the expression and function of the AR by POH. through inhibition of androgen-induced cell growth and androgen-stimulated secretion of prostate-specific antigen and hK2, in human pCa cell line LNCaP. In addition, we demonstrated, for the first time, that POH inhibits the transcription activities of the AR gene promoter by over-expression of c-Jun protein. These novel properties of POH strongly suggest that POH could be highly useful for intervention of pCa.
Revue / Journal Title
Cancer letters ISSN 0304-3835 CODEN CALEDQ
Source / Source
2006, vol. 236, no2, pp. 222-228 [7 page(s) (article)]
Langue / Language
Anglais

Editeur / Publisher
Elsevier, Shannon, IRLANDE (1975) (Revue)

Mots-clés d’auteur / Author Keywords
Perillyl alcohol ; Androgen receptor ; Prostate carcinoma cell line LNCaP ;
Localisation / Location
INIST-CNRS, Cote INIST : 17217, 35400015310684.0080

Sources of perillyl alcohol:

http://www.naturalstandard.com/index-abstract.asp?create-abstract=/monographs/herbssupplements/patient-perillylalcohol.asp

"Related Terms:
l-perillyl alcohol, monoterpene, monoterpene perillyl alcohol, perilla, perillic acid, POH.

Perillyl alcohol is isolated from the essential oils of several plants including cherries, lavender, peppermint, spearmint, celery seeds, sage, cranberries, lemongrass, ginger grass, savin juniper, Conyza newii, caraway, Perilla frutescens, and wild bergamont.
Animal studies suggest that perillyl alcohol may help slow growth of pancreatic, mammary, and liver tumors. It may also help colon, lung, and skin cancer. Perillyl alcohol is under sponsorship from the National Cancer Institute (NCI), and is undergoing phase II clinical trials."

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Well, this is a weird one.

I don’t know exactly how they intend to get the stuff into the body and target it to where they want it, though. Otherwise it sounds like just another systemic antiandrogen.

But that bit about “inhibits transcription of the AR gene” . . .

I wonder if that might be the phrase that really makes this mean something larger. That sounds like maybe an influence on gene expression itself has been demonstrated, not just an effect on the practical efficacy of the existing ARs.

3

» Well, this is a weird one.
»
» I don’t know exactly how they intend to get the stuff into the body and
» target it to where they want it, though. Otherwise it sounds like just
» another systemic antiandrogen.
»
»
»
»
»
» But that bit about “inhibits transcription of the AR gene” . . .
»
» I wonder if that might be the phrase that really makes this mean something
» larger. That sounds like maybe an influence on gene expression itself has
» been demonstrated, not just an effect on the practical efficacy of the
» existing ARs.

Cal, did you see this part? :

Perillyl alcohol is isolated from the essential oils of several plants including cherries, lavender, peppermint, spearmint, celery seeds, sage, cranberries, lemongrass, ginger grass, savin juniper, Conyza newii, caraway, Perilla frutescens, and wild bergamont.

The “experiment” I conducted a couple of years ago, where I put peppermint oil/purified water on one half of my chin at about a 1/40 ratio severely reduced the whiskers on that side of the face to less than half (probably about a third) of the growth on the untreated side. There was no inflammation. I worried that the peppermint might be “bad” for hair in some untoward way because the result was so profoundly strong. Well the whiskers are about equal now on both sides of the chin again…so there was no lasting damage. There are things upstream in androgen skin metabolism of both testosterone and DHT. Either peppermint must inhibit both of them, or it must really act against the receptor. American Crew Thickening Shampoo and American Crew Citrus Mint Shampoo both use peppermint. Paul Mitchell Tea Tree uses peppermint. Alpecin uses menthol. Tricomin Shampoo uses peppermint. Jason’s Tea Tree shampoo uses peppermint. These entities apparently think that peppermint must not be “bad” for hair. I can assure you its a credible anti-androgen via the Turkish Hirsutism study. It worked against hirsutism in women, and men who drank peppermint tea complained of low libido. A Japanese Study found that peppermint (and clove, and licorice) all inhibited alpha five reductase in human skin and lessened sebum secretions (google it). Maybe the stuff is a winner after all…

BTW-----Ive got my fluridil now, and am testing it. I did the first application to the forehead yesterday. In six more days…I’ll sebutape it and see what I got. Cedarwood wasn’t a winner. I think cedarwood might need a carrier oil like they used in the Scottish Alopecia Areata Study (they used both Jojoba and Grapeseed oils as “carriers” because of their penetration ability). When I tested the peppermint oil/water, I used no carrier, so whatever molecules that have the anti-androgenic effect must be small.

4

Yeah, I noticed the sources of that type of alcohol have a common thread. Funny how that works, eh? The primitive peoples knew what they were doing yet again.

So your peppermint growth experiment didn’t show lasting damage to the growth after all? It just took a LONG time for the test spot to revert to its pre-pepperminted condition?

Well, my gut reaction, of course, is: “So why can’t we slather our whole scalps in the stuff, and finally have our fabled perfect topical anti-androgen?”

And then my next question is about the systemic effects of that idea . . .

5

?
»
»
»
»
» And then my next question is about the systemic effects of that idea . . .

That would certainly be a concern. I didn’t get sides, but I was only putting it on one half of my chin.

Tricomin Shampoo uses peppermint oil. It says to leave on for three-to-five minutes on the instructions. If you wanted to “kinda” try it, that would be a good way to do so without any hassle as folks shampoo anyway. To my knowledge, nobody has ever taken a before-after-photo of the tricomin shampoo results, but there are a couple of regrowth photos on tricomin’s website after two men “used tricomin products” in clincal tests,
http://tricomin.com/pages/why.html (bottom of the page, if you move the cursor over the image, you get the second set of images of another man).

The reason I wonder about the old traditional hair remedies like the cedarwood, lavender, rosemary, thyme that were used in the Scottish Essential Oils Alopecia Areata study is that those must have been “discovered” over thousands of years of trial-and-error. They’ve been used since way-on-back. Scottish mummies found in a peat bog from the iron age had cedarwood oil in their hair. I was trying to figure out why. The only other reason that the one given (hair pomade…of which cedarwood would make an awful one), was cedarwoods anti-insect/mosquito effect (in some patents for that).

Ill know about fluridil in about 6 more days…

6

What impresses me about the peppermint example is that you got that inhibition of beard growth for so damn long afterward. I remember that. For a while you were worried it would be permanent.

Even if topical peppermint does go systemic and cause sides, I still have a hard time imagining one of these substances having long-term systemic effects in proportion to the growth inhibition that you got from that test. Do you have any thoughts on this? The only thing putting the brakes on my suspicions here, is that I would expect an effect that beneficial to be already well known. (Why didn’t Tricomin’s testing find it out? Why aren’t they selling a stronger dosage if it works this well?)

But so far I think all these natural topical options that I’ve tried have a real systemic problem. At least for me. Lavendar oil had some, and Tea Tree oil definitely did.

Maybe not all guys have systemic effects from these things, but then again not every guy has systemic effects from oral Finasteride either.

7

» What impresses me about the peppermint example is that you got that
» inhibition of beard growth for so damn long afterward. I remember that.
» For a while you were worried it would be permanent.

You know what man? I have a beard now, and was looking at it in the mirror from a distance and something occured to me…my right side -still- isn’t as dark as the left in the chin area. You are right, its not quite caught up even now. I ran my finger over one side vs. the other and the right side still feels weaker and the hairs still aren’t quite as dark (my beard is about like Brad Pitts, dark brown on the chin, light brown on the cheeks, hair is light brown. Maybe pepperimint, until its shown to help regrowth -alone- would be best passed over for something else at this point. »
»
»
»
»
» But so far I think all these natural topical options that I’ve tried have
» a real systemic problem. At least for me. Lavendar oil had some, and Tea
» Tree oil definitely did. Several guys seem to get sides from tea tree oil shampoos…maybe that molecule is small enough to really get through and doesn’t degenerate into something else before giving a guy sides…Ive heard this complaint three or four times in regards to tea tree.

Note: Maybe a guy could just shampoo with lavender body washes (the kinds that caused gyno on those pre-pubertal boys). It would be cheap, and we -know-they can penetrate if left on long enough. My guess is that they need to be left on for a few minutes as kids bathing in tubs are usually in there a while»

I just put some more fluridil above my left eyebrow. Im anxious to see if this stuff has effect. I’ll sebutape it and see this weekend. If it doesn’t, Spiro is about all thats left. My crinagen I ordered never has shown up at my door. If nothing works, I’ll be on finas, nizoral until something is fda approved and will give up researching it and focus on the wounding stuff in the time being.

8

» You know what man? I have a beard now, and was looking at it in the
» mirror from a distance and something occured to me…my right side
» -still- isn’t as dark as the left in the chin area. You are right, its not
» quite caught up even now. I ran my finger over one side vs. the other and
» the right side still feels weaker and the hairs still aren’t quite as dark
» (my beard is about like Brad Pitts, dark brown on the chin, light brown on
» the cheeks, hair is light brown. Maybe pepperimint, until its shown to help
» regrowth -alone- would be best passed over for something else at this
» point.

There’s no “old wives tales” or herbal remedy stories about Peppermint as a baldness fighter as far as I know. That’s bad.

But then again, I can’t recall any stories about Peppermint’s usefulness as a body/facial hair REMOVER, either. And that property of the stuff seems real enough . . .

» Several guys seem to get sides from tea
» tree oil shampoos…maybe that molecule is small enough to really
» get through and doesn’t degenerate into something else before giving a guy
» sides…Ive heard this complaint three or four times in regards to tea
» tree.

TTO worked like hell on my hair, and also gave me systemic sides for sure. LO did less hair good and I’m not sure it caused me any real sides.

Sounds like evidence that this is just another trade off between hair gains and systemic sides.

» Note: Maybe a guy could just shampoo with lavender body washes (the
» kinds that caused gyno on those pre-pubertal boys). It would be cheap, and
» we -know-they can penetrate if left on long enough. My guess is that they
» need to be left on for a few minutes as kids bathing in tubs are usually in
» there a while.

It’s not a bad idea at all. If nothing else, this may be the cheapest/easiest/most practical topical AA we’ve found yet.

» I just put some more fluridil above my left eyebrow. Im anxious to see if
» this stuff has effect. I’ll sebutape it and see this weekend. If it
» doesn’t, Spiro is about all thats left. My crinagen I ordered never has
» shown up at my door. If nothing works, I’ll be on finas, nizoral until
» something is fda approved and will give up researching it and focus on the
» wounding stuff in the time being.

I haven’t read much about Fluridil. Best of luck with that one.

BTW, I have fully quit Fin now. (F*ck it. Either I nail down the Folica method soon, or I go balder while I save up for a transplant.)

I tapered down from Fin VERY gradually between about December and March. I’ve still got mild side effects from it even now, but they’re maybe half as bad as they were when I was on the stuff. Seems to be reversing very gradually.

If you ever need to quit the stuff, I would TOTALLY advocate the taper-down approach with a gradual spacing out of the days between the dosages at the end of it. This quitting pattern really spared me the hormonal rollercoaster. (And I KNOW that I would have suffered from a coaster ride otherwise, because I had always started to feel it every time I had quit the stuff temporarily in the past.)

9

I am currently using lavender oil (because of its anti-androgenic and pro-estrogenic effects) in my minoxidil for like three months now, and so far I am very pleased with it. It totally stopped my hairloss and some hair started to grow on my temples and existing hair thickened up. I have a nw2-type hairline and some thinning overall. Btw I use finasteride too, but fin and minox I am using for several years now, but with no such great results. No sides.