Curcumin, androgen receptor antagonist.......study...

[michael barry]

Titre du document / Document title
Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines
Auteur(s) / Author(s)
NAKAMURA Keiichiro (1) ; YASUNAGA Yutaka (1) ; SEGAWA Takehiko (1) ; DAEJIN KO (1) ; MOUL Judd W. (1) ; SRIVASTAVA Shiv (1) ; RHIM Johng S. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, ETATS-UNIS

Résumé / Abstract
Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-KB (NF-KB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-KB and CBP).
Revue / Journal Title
International journal of oncology ISSN 1019-6439
Source / Source
2002, vol. 21, no4, pp. 825-830





Nosy as I am, I took Harold's suggestion to heart and tried to mix some curcumin with my shampoo. It made it (L'Oreal Vive) turn from white to a beige, but it really did seem to be soluble in the shampoo when I stirred it up in the palm of my hand. I used it with no problems. ..........................I also attempted to mix some curcumin (maybe 2-3% at most, with some cetaphil lotion). After half an hour, despite quite a bit of stirring, the small granules of curcumin are still visible in the now light beige cream. I'll wait overnight and see if the oils in the cream dissolve the curcumin, but Im kind of inclined to doubt it. The GOOD NEWS IS....................I think you can put a pinch of curcumin in your shampoo, mix it up with you finger until its consistent, and use. I dont know how long you might have to leave it in to absorb or if it will absorb though...................it would seem a curcumin topical should be helpful in AA though.

 

[Follically Challenged]

TYVM Michael Barry, as always.

Before you've stated that you thought the orange curcumin would be more potent than white curcumin...what led you to that conclusion? TIA

 

[michael barry]

TABLE 5
Inhibition of 5 α-reductase isozymes by curcumin and related
compoundsa
5 α-Reductase
Whole-cell
Cell-Free assay IC50 (µM) assay IC50 (µM)
Compound Type 1 Type 2 Type 1 Type 2
Curcumin 3 (95) 5 (87) 9 (99) 7 (99)
Tetrahydrocurcumin 80 (56) 29 (73) NDb NDDemethoxy- >100 (23) >100 (42) ND ND
tetrahydrocurcumin
4-hydroxy-3- >100 (10) >100 (-60) ND ND
methoxy-
cinnamaldehyde
Coniferol >100 (10) 100 (49) ND ND
4-(4-hydroxy-3- >100 (3) >100 (4) ND ND
methoxyphenol)-3-
buten-2-one
Ferulic Acid >100 (0) >100 (18) ND ND
Capsaicin >100 (0) >100 (8) ND ND
Eugenol >100 (0) 100 (50) ND ND



dont know if tetrahydrocurcumin is the same as white curcumin.............................so for now, I guess I'd go with orange/yellow until I knew more.

 

[goata007]

Look what I found:

http://www.lef.org/magazine/mag2006/jun2006_report_sunscreen_02.htm

Some of the recently discussed ingredients are on this list i.e Green tea extract, curcumin, licorice, and Rosemary extract. As of tetrahydrocurcumin, the article says its an effective skin lightening agent!

 

[Follically Challenged]

Thanks Michael. I went to http://www.skinactives.com and found this:

Tetrahydrocurcuminoids

The chemical modification of curcuminoids, the powerful actives in tumeric (Curcuma longa) make it easier to incorporate them in cosmetics. The original strong yellow becomes white, at the same time facilitating the use of this anti-oxidant, anti-inflammatory active by the skin.

http://www.skinactives.com/products/thc.hair transplant

It also says Tetrahydrocurcuminoids are a skin lightener....sounds like bad news for hair?

 

[alkulk]

It also says Tetrahydrocurcuminoids are a skin lightener....sounds like bad news for hair?

Why?

 

[Follically Challenged]

It also says Tetrahydrocurcuminoids are a skin lightener....sounds like bad news for hair?

Why?

From my limited understanding of the human body, the skin colours itself the same way hair gets coloured...by melanocytes. So, curcumin may be great for hair growth, the problem with it might be is it makes yours hair white over time.

 

[alkulk]

Ah, I see...

 

[michael barry]

Follicularily Challenged brings up a good point.........


Both Curcumin and Licorice lighten the skin and are in skin-lightening products.


Licorice, even though being very anti-androgenic and inhibiting alpha five reductase AND inhibiting androgen receptors, seems to do something that is bad for hair period as rat-neck hair has shown in experiments.

I HOPE that curcumin doesn't do something that is bad for hair period also......................that is a concern.

Curcumin inhibited both forms of alpha five reductase at 99% in whole cell assays and inhibited hamster flank organs by 87% (the same as gamma linolenic acid), and inhibited about 37% of flank organ growth when pure DHT was applied (indicating that it inhibits the receptor directly to some extent). We know, via androscience, that continual application of curcumoids seem to degrade the androgen receptors period by interfereing with certain protiens within them.


I hope Curcumin will be "good" for hair though.........................




If I had to guess right now, the safest thing to add to one's shampoo would be gel caps of soy isoflavones. They decrease androgen receptor expression and genistein and daidzien both inhibited whole cell assays of alpha five type two at close to ninety percent, and had some inhibition of type one also. Topical soy decreased sebum excretions by 65% at week five, indictating anti-androgenic potency in human skin at least at the sebaceous gland level....................but admittedly anagen hair follicles are definitely deeper in the dermis than that.

 

[el_duterino]

thanks so much for all this info, Michael
So we can speculate that this ASC-J9 foam can possibly also discolor or grey-out existing hair then ?

 

[HARM1]

Follicularily Challenged brings up a good point.........


Both Curcumin and Licorice lighten the skin and are in skin-lightening products.


Licorice, even though being very anti-androgenic and inhibiting alpha five reductase AND inhibiting androgen receptors, seems to do something that is bad for hair period as rat-neck hair has shown in experiments.

I HOPE that curcumin doesn't do something that is bad for hair period also......................that is a concern.

Curcumin inhibited both forms of alpha five reductase at 99% in whole cell assays and inhibited hamster flank organs by 87% (the same as gamma linolenic acid), and inhibited about 37% of flank organ growth when pure DHT was applied (indicating that it inhibits the receptor directly to some extent). We know, via androscience, that continual application of curcumoids seem to degrade the androgen receptors period by interfereing with certain protiens within them.


I hope Curcumin will be "good" for hair though.........................




If I had to guess right now, the safest thing to add to one's shampoo would be gel caps of soy isoflavones. They decrease androgen receptor expression and genistein and daidzien both inhibited whole cell assays of alpha five type two at close to ninety percent, and had some inhibition of type one also. Topical soy decreased sebum excretions by 65% at week five, indictating anti-androgenic potency in human skin at least at the sebaceous gland level....................but admittedly anagen hair follicles are definitely deeper in the dermis than that.

You say buy small soy pills, cut them open and add them to my nizoral?

 

[michael barry]

adding soy isoflavone pills (drained in your shampoo) ought to be helpful in my opinon.......................topical soy isoflavones decreased sebum secretions by sixty five percent in one experiment...................leave the suds in for a couple of minutes on a warm hydrated scalp, and I see no reason for some absorbtion not to be taking place.......

Make sure you mix the shampoo and isoflavones (gel caps) up really good in your hand until the solution is really mixed well......it "ought" to be helpful anyway. Both genistein and daidzien were very effective WHOLE cell alpha five reducatase type two inhibitiors and genistein decreases androgen receptor expresssion.

 

[HARM1]

adding soy isoflavone pills (drained in your shampoo) ought to be helpful in my opinon.......................topical soy isoflavones decreased sebum secretions by sixty five percent in one experiment...................leave the suds in for a couple of minutes on a warm hydrated scalp, and I see no reason for some absorbtion not to be taking place.......

Make sure you mix the shampoo and isoflavones (gel caps) up really good in your hand until the solution is really mixed well......it "ought" to be helpful anyway. Both genistein and daidzien were very effective WHOLE cell alpha five reducatase type two inhibitiors and genistein decreases androgen receptor expresssion.

Cutting away small pills sounds expensive and hard work, don't you think? and who is to say that 1) you soy capsules have genistein and daidzien 2) that the isoflavones don't disrupt the nizoral?

isn't there a more efficient and cheap way? like a big box of soy isoflavones in liquid form?

 

[michael barry]

the pills were soy ISOFLAVONE gel caps............the amount of genistein and daidzien were printed on the bottle

the contents are liquid--more of a syrupy concoction than a liquid---about the consistency of hair conditioner

 

[Follically Challenged]

the pills were soy ISOFLAVONE gel caps............the amount of genistein and daidzien were printed on the bottle

the contents are liquid--more of a syrupy concoction than a liquid---about the consistency of hair conditioner

What brand?

 

[HARM1]

the pills were soy ISOFLAVONE gel caps............the amount of genistein and daidzien were printed on the bottle

the contents are liquid--more of a syrupy concoction than a liquid---about the consistency of hair conditioner

michael you must explain: "the pills were soy ISOFLAVONE gel caps" - you mean in the patnent study? I didn't see any mentioning of gel caps. The work is done using a product called "total soy". when you write gel cap you mean this right?

You're saing they just bought soy gel caps, cut them and applied them ? Oo

 

[michael barry]

IM not talking about the experiment, Im talking about what I think would work. I used to have some soy isoflavone gel caps,,,,,,,,,,,,,I think from Natures way. Its been a while since I had them, but the genisteien and Daidzien content were printed right on the bottle in per-capsule info. IT was alot of it in each capsule.



Meanwhiles Hairsite posted this new study:



Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia

Growth Horm IGF Res. 2007 Oct;17(5):408-15

OBJECTIVE:
Insulin-like growth factor-I (IGF-I) plays an important role in hair growth. Capsaicin activates vanilloid receptor-1, thereby increasing the release of calcitonin gene-related peptide (CGRP) from sensory neurons, and CGRP has been shown to increase IGF-I production.

We recently reported that isoflavone, a phytoestrogen, increases production of CGRP by increasing its transcription in sensory neurons. These observations raise the possibility that administration of capsaicin and isoflavone might promote hair growth by increasing IGF-I production. In the present study, we examined this possibility in mice and humans with alopecia.


DESIGN:
Dermal IGF-I levels, immunohistochemical expression of IGF-I in the skin and hair regrowth were examined after capsaicin and isoflavone administration to wild-type (WT) mice and CGRP-knockout mice. Plasma levels of IGF-I and promotion of hair growth were evaluated in 48 volunteers with alopecia after administration of capsaicin and isoflavone for 5 months.


RESULTS:
Subcutaneous administration of capsaicin significantly increased dermal IGF-I levels at 30 min after administration in WT mice (p < 0.01), but not in CGRP-knockout mice. Dermal levels of IGF-I were significantly higher in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks (p < 0.01) and in those administered neither of them (p < 0.01).

Immunohistochemical expression of IGF-I at dermal papillae in hair follicles was increased in WT mice administered capsaicin and isoflavone and in those administered capsaicin alone at 4 wks. Hair regrowth was clearly more accelerated in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks and in those administered neither of them.

Plasma levels of IGF-I were significantly increased from baseline levels in 31 volunteers with alopecia at 5 months after oral administration of capsaicin (6 mg/day) and isoflavone (75 mg/day) (p < 0.01), while they were not increased in 17 volunteers with alopecia administered placebo.

The number of volunteers with alopecia who showed promotion of hair growth at 5 months after administration was significantly higher among volunteers administered capsaicin and isoflavone (20/31: 64.5%) than among those administered placebo (2/17: 11.8%) (p < 0.01).

CONCLUSIONS:

These observations strongly suggested that combined administration of capsaicin and isoflavone might increase IGF-I production in hair follicles in the skin, thereby promoting hair growth. Such effects of capsaicin and isoflavone might be mediated by sensory neuron activation in the skin. ---

 

[Follically Challenged]

Excellent post Michael Barry. When I round up some ducats I'm going to put together a topical largely inspired by your posts. Thank you.

 

[harold]

thanks so much for all this info, Michael
So we can speculate that this ASC-J9 foam can possibly also discolor or grey-out existing hair then ?

We can speculate but thats it. A quick search on melanocytes, melanin and curcumin turned up nothing.
Actually scratch that....

Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells.
Marín YE, Wall BA, Wang S, Namkoong J, Martino JJ, Suh J, Lee HJ, Rabson AB, Yang CS, Chen S, Ryu JH.

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Melanoma, the most deadly form of skin cancer, is very aggressive and resistant to present therapies. The transcription factor nuclear factor-kappa B (NF-kappaB) has been reported to be constitutively active in many types of cancer. Constitutively active NF-kappaB seen in melanoma likely plays a central role in cell survival and growth. We have established and characterized novel cell lines from our murine melanoma model. Here we report the constitutive activity of NF-kappaB in these melanoma-derived cells, as shown by electrophoretic mobility shift assay and reporter assays. We hypothesized that agents that inhibit NF-kappaB may also inhibit cell proliferation and may induce apoptosis in such melanoma cells. Curcumin has been shown to inhibit NF-kappaB activity in several cell types. In our system, curcumin selectively inhibited growth of melanoma cells, but not normal melanocytes. Curcumin induced melanoma cells to undergo apoptosis, as shown by caspase-3 activation, inversion of membrane phosphatidyl serine, and increases in cells in the sub-G1 phase. A curcumin dose-dependent inhibition of NF-kappaB-driven reporter activity correlated with decreased levels of phospho-IkappaBalpha, and decreased expression of NF-kappaB-target genes COX-2 and cyclin D1. This study demonstrates that the use of cells from our model system can facilitate studies of signaling pathways in melanoma. We furthermore conclude that curcumin, a natural and safe compound, inhibits NF-kappaB activity and the expression of its downstream target genes, and also selectively induces apoptosis of melanoma cells but not normal melanocytes. These encouraging in-vitro results support further investigation of curcumin for treatment of melanoma in vivo.

hh

 

[Follically Challenged]

*Bows to Harold's greatness*