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Sulforaphane destabilizes the androgen receptor in prostate cancer cells
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funes
hadrion
CausticSymmetry
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Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16663-8. Epub 2009 Sep 15.
Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6.
Gibbs A, Schwartzman J, Deng V, Alumkal J.
Division of Hematology and Oncology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
High consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer in epidemiological studies. There is preliminary evidence that sulforaphane, derived from glucoraphanin found in a number of crucifers, may prevent and induce regression of prostate cancer and other malignancies in preclinical models, but the mechanisms that may explain these effects are not fully defined. Recent reports show that sulforaphane may impair prostate cancer growth through inhibition of histone deacetylases, which are up-regulated in cancer. Indeed, one of these enzymes, histone deacetylase 6 (HDAC6), influences the acetylation state of a key androgen receptor (AR) chaperone, HSP90. AR is the central signaling pathway in prostate cancer, and its inhibition is used for both prevention and treatment of this disease. However, it is not known whether the effects of sulforaphane involve suppression of AR. We hypothesized that sulforaphane treatment would lead to hyperacetylation of HSP90 and that this would destabilize AR and attenuate AR signaling. We confirmed this by demonstrating that sulforaphane enhances HSP90 acetylation, thereby inhibiting its association with AR. Moreover, AR is subsequently degraded in the proteasome, which leads to reduced AR target gene expression and reduced AR occupancy at its target genes. Finally, sulforaphane inhibits HDAC6 deacetylase activity, and the effects of sulforaphane on AR protein are abrogated by overexpression of HDAC6 and mimicked by HDAC6 siRNA. The inactivation by sulforaphane of HDAC6-mediated HSP90 deacetylation and consequent attenuation of AR signaling represents a newly defined mechanism that may help explain this agent's effects in prostate cancer.
Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6.
Gibbs A, Schwartzman J, Deng V, Alumkal J.
Division of Hematology and Oncology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
High consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer in epidemiological studies. There is preliminary evidence that sulforaphane, derived from glucoraphanin found in a number of crucifers, may prevent and induce regression of prostate cancer and other malignancies in preclinical models, but the mechanisms that may explain these effects are not fully defined. Recent reports show that sulforaphane may impair prostate cancer growth through inhibition of histone deacetylases, which are up-regulated in cancer. Indeed, one of these enzymes, histone deacetylase 6 (HDAC6), influences the acetylation state of a key androgen receptor (AR) chaperone, HSP90. AR is the central signaling pathway in prostate cancer, and its inhibition is used for both prevention and treatment of this disease. However, it is not known whether the effects of sulforaphane involve suppression of AR. We hypothesized that sulforaphane treatment would lead to hyperacetylation of HSP90 and that this would destabilize AR and attenuate AR signaling. We confirmed this by demonstrating that sulforaphane enhances HSP90 acetylation, thereby inhibiting its association with AR. Moreover, AR is subsequently degraded in the proteasome, which leads to reduced AR target gene expression and reduced AR occupancy at its target genes. Finally, sulforaphane inhibits HDAC6 deacetylase activity, and the effects of sulforaphane on AR protein are abrogated by overexpression of HDAC6 and mimicked by HDAC6 siRNA. The inactivation by sulforaphane of HDAC6-mediated HSP90 deacetylation and consequent attenuation of AR signaling represents a newly defined mechanism that may help explain this agent's effects in prostate cancer.
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Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Here's my question IH -- Is taking Sulforaphane possibly as effective as just consuming broccoli? I'm not a broccoli fan and I don't eat it nearly enough (certainly not everyday).
I'm just curious if you think the extract is as effective or more effective than the whole food.
I'm just curious if you think the extract is as effective or more effective than the whole food.
hadrion- Posts : 776
Join date : 2008-07-09
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
hadrion - In the form of Broccoli sprouts, not regular broccoli is the best source of Sulforaphane. Personally, I'm not a fan of regular Broccoli, but Broccoli sprouts in my opinion taste better, and are very easy to eat. They are great in salads and sandwiches and the like.
Broccoli sprouts contain up to 50 times more Sulforaphane than Broccoli and they are extremely bioavailable, more so than supplements in this case. I've looked into this issue before and I recall that a modest amount of daily consumption of the sprouts only would give you a solid dose of Sulforaphane.
Here's a photo of the sprouts
http://www.broccosprouts.com/img2/photo/pkg1_b_350.jpg
Broccoli sprouts contain up to 50 times more Sulforaphane than Broccoli and they are extremely bioavailable, more so than supplements in this case. I've looked into this issue before and I recall that a modest amount of daily consumption of the sprouts only would give you a solid dose of Sulforaphane.
Here's a photo of the sprouts
http://www.broccosprouts.com/img2/photo/pkg1_b_350.jpg
_________________
My regimen
http://www.immortalhair.org/mpb-regimen
Now available for consultation (hair and/or health)
http://www.immortalhair.org/health-consultation
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
I've used the sprouts before in salads and when I was juicing. I guess I should make it a point to get them in everyday. I'm taking the broccomax supp, but I've always been a little skeptical on taking broccoli in a pill form vs. the whole food form.
hadrion- Posts : 776
Join date : 2008-07-09
the italian way ...
I'm italian, and in my country we are fond of this recipe:
Orecchiette with Broccoli Rabe, or Orecchiette con Cime di Rapa: There are many recipes for this signature dish from Puglia. This particular one is quick and simple. To serve 4 you'll need:
Prep Time: 20 min
Cook Time: 20 min
Ingredients:
1 pound (500 g) orecchiette
2 1/4 pounds (1 k) broccoli rabe
1 hot pepper, shredded
2 cloves garlic, minced
6 tablespoons olive oil
Grated Pecorino Romano (not too sharp)
Preparation:
Pick over and clean the broccoli. Bring a pot of water to a boil, salt it, add the broccoli, and after a few minutes stir in the orecchiette and cook the two together until the orecchiette are done.
While the pasta's cooking, simmer the garlic and the pepper in the oil, taking care lest the garlic brown and become bitter. Drain the pasta and broccoli well, turn them out into the skillet with the oil and garlic, cook, stirring, for a few seconds to distribute the seasoning evenly, and serve with grated cheese.
The recipe call for "cime di rapa" (brassica rapa sylvestris), but I can tell you that the ordinary broccoli sprouts are fine too. I'm italian, I can't be wrong :-)
Orecchiette with Broccoli Rabe, or Orecchiette con Cime di Rapa: There are many recipes for this signature dish from Puglia. This particular one is quick and simple. To serve 4 you'll need:
Prep Time: 20 min
Cook Time: 20 min
Ingredients:
1 pound (500 g) orecchiette
2 1/4 pounds (1 k) broccoli rabe
1 hot pepper, shredded
2 cloves garlic, minced
6 tablespoons olive oil
Grated Pecorino Romano (not too sharp)
Preparation:
Pick over and clean the broccoli. Bring a pot of water to a boil, salt it, add the broccoli, and after a few minutes stir in the orecchiette and cook the two together until the orecchiette are done.
While the pasta's cooking, simmer the garlic and the pepper in the oil, taking care lest the garlic brown and become bitter. Drain the pasta and broccoli well, turn them out into the skillet with the oil and garlic, cook, stirring, for a few seconds to distribute the seasoning evenly, and serve with grated cheese.
The recipe call for "cime di rapa" (brassica rapa sylvestris), but I can tell you that the ordinary broccoli sprouts are fine too. I'm italian, I can't be wrong :-)
funes- Posts : 9
Join date : 2009-08-10
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
CausticSymmetry, do you have an idea of how much a modest in take is?
A qualified guess: From 50 to 100 gram sprouts to get 30 mg sulforaphane.
A qualified guess: From 50 to 100 gram sprouts to get 30 mg sulforaphane.
CausticSymmetry wrote:hadrion - In the form of Broccoli sprouts, not regular broccoli is the best source of Sulforaphane. Personally, I'm not a fan of regular Broccoli, but Broccoli sprouts in my opinion taste better, and are very easy to eat. They are great in salads and sandwiches and the like.
Broccoli sprouts contain up to 50 times more Sulforaphane than Broccoli and they are extremely bioavailable, more so than supplements in this case. I've looked into this issue before and I recall that a modest amount of daily consumption of the sprouts only would give you a solid dose of Sulforaphane.
Here's a photo of the sprouts
http://www.broccosprouts.com/img2/photo/pkg1_b_350.jpg
Amaranthaceae- Posts : 1368
Join date : 2008-07-15
Location : Copenhagen
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
cpio - Broccoli sprouts contain 250 milligrams of sulforaphane glucosinolate per 100 grams per serving. So that's 2.5 milligrams per gram. The good news is that the antioxidant effect lasts for longer than a day, but apparently for a few days. I'll have to look it up to be certain just how long it lasts for.
10 grams supplying 25 mg sounds about right.
10 grams supplying 25 mg sounds about right.
_________________
My regimen
http://www.immortalhair.org/mpb-regimen
Now available for consultation (hair and/or health)
http://www.immortalhair.org/health-consultation
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Thats what I call a super-food!
Hmm .. Possibly grow them at home in the window ledge.
Hmm .. Possibly grow them at home in the window ledge.
Amaranthaceae- Posts : 1368
Join date : 2008-07-15
Location : Copenhagen
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Growing at home would be the most economical option. The stores charge a boat load for them.
hapyman- Posts : 697
Join date : 2008-11-11
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Guys, there's definitely something going for the power of broccoli sprouts as far as my own experience tells me. I posted this before but I thought I'd tell everyone again as I am convinced of the benefits of this plant. Everyday for the past three months I blend a handful of broccoli spouts together with a handful of rocket leaves in water and drink it. The reason I do this is I have a history of digestive problems which I attribute to H. Pylori. Both broccoli sprouts and rocket are proven to fight H. Pylori, and since I've been doing this my problems have definitely gone away. Tastes terrible but what do you do. Another bonus I attribute to it is that it has had a significant positive effect on my hair and general wellbeing. I think it has even improved my breathing capacity when I do cardio training - any thoughts on this IH? I certainly thank IH for guiding me into the direction of broccoli sprouts through his recommendation of Broccomax.
Anyone, who suffers from digestive problems, ulcers, H. Pylori infection etc would do well to taking this very simple mixture on a daily basis. If you don't have these problems, I would still take it as a general tonic and cancer preventative. Anything this green must be good for you! In particular, I hope someone tries this for themselves and report back on its effectiveness after a few weeks - I would be really interested if it works for others as it has for me.
Anyone, who suffers from digestive problems, ulcers, H. Pylori infection etc would do well to taking this very simple mixture on a daily basis. If you don't have these problems, I would still take it as a general tonic and cancer preventative. Anything this green must be good for you! In particular, I hope someone tries this for themselves and report back on its effectiveness after a few weeks - I would be really interested if it works for others as it has for me.
Grateful- Posts : 169
Join date : 2008-07-19
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
Grateful - Sulforaphane research has been amazing in the last year, everything from skin and hair health, to cardiovascular and lung health, to prostate health, not to mention the digestive benefits. I think part of the secret to this nutrient is that it restores innate antioxidant protection to various body systems.
Sulforaphane is becoming a classical epigenetic modulator, capable of redirecting genetic expression. It does everything from histone deacetylase (HDAC) inhibition (useful in cancer prevention), protects against glutathione degradation (useful in Parkinson's prevention), improves phase II detoxification significantly, protects against atherosclerosis by restoring Nrf2 status in the endothelium, blunts the androgen receptor in prostatic cancer, and protects keratinocytes from depletion of antioxidant capacity--this last part is especially interesting for hair growth.
I could go on and on, I believe it even protects the skin against atopic dermatitis (eczema), by modulating skin immunity.
Sulforaphane is becoming a classical epigenetic modulator, capable of redirecting genetic expression. It does everything from histone deacetylase (HDAC) inhibition (useful in cancer prevention), protects against glutathione degradation (useful in Parkinson's prevention), improves phase II detoxification significantly, protects against atherosclerosis by restoring Nrf2 status in the endothelium, blunts the androgen receptor in prostatic cancer, and protects keratinocytes from depletion of antioxidant capacity--this last part is especially interesting for hair growth.
I could go on and on, I believe it even protects the skin against atopic dermatitis (eczema), by modulating skin immunity.
_________________
My regimen
http://www.immortalhair.org/mpb-regimen
Now available for consultation (hair and/or health)
http://www.immortalhair.org/health-consultation
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
I love this stuff already!
Amaranthaceae- Posts : 1368
Join date : 2008-07-15
Location : Copenhagen
Re: Sulforaphane destabilizes the androgen receptor in prostate cancer cells
I'm definitely going to have to add broccoli spouts as a staple part in my diet from now on. The benefits seem to good to ignore, I'll just have to start growing them i think.
Silverlin- Posts : 365
Join date : 2008-07-15
Age : 36
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