Enhanced Androgen receptor (AR) activity has been conclusively shown to be an integral component of Acne, Androgenetic Alopecia, (AGA), and Prostate Enlargement (BPH) and Cancer. Several treatments for AGA and Acne in the Biotech developmental pipeline specifically target the Androgen receptor. Notable among them is the much anticipated, Curcumin analogue, ASC-J9, developed by Androscience, which functionally works as a lasting cure by gradually ablating the AR. ASC-J9, also has systemic indications for the treatment of Prostate cancer and BPH. In a recent study the combination of Soy Isoflavones and Curcumin, both mainstays in our treatment protocol, suppressed AR activity. Pharmaceutical androgen receptor blockers include Spironolactone and Cyproterone Acetate, neither of which can be systemically used in men because of their side effects. Green Tea, conversely has been shown to actually have libido enhancing effects, and helps to prevent gynecomastia (male breast enlargement) due to its aromatase inhibiting properties. Green Tea also regulates levels of SHBG, which are lower in balding vs. nonbalding men. Mega Green Tea Extract, which we’ve been recommending for years has the highest commercial available mg dose of EGCG per capsule, (326.25 mg). One capsule has the polyphenol equivalent of 10 cups of brewed Green Tea, making Mega Green Tea Extract a far more convenient and cost effective alternative to the relatively expensive, not to mention bladder busting option of drinking that quantity of tea on a daily basis.
Internally consumed Green Tea also provides anti-aging benefits to skin, acting as an internal UV protectant. The absorption of EGCG can be significantly enhanced by the concurrent usage of a few drops of lemon or lime juice, and/or ascorbic acid,(vitamin C). The myriad of health, chemoprevention and anti-aging benefits of Green Tea go well beyond the scope of this article. We decided to focus on the documented dermatological mechanisms and benefits in response to its internal consumption.
FASEB J. 2010 Dec 21. [Epub ahead of print]
Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.
Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H.
Department of Dermatology, University of Wisconsin, Madison, Wisconsin, USA.
Androgen deprivation therapy is the major treatment for advanced prostate cancer (PCa). However, it is a temporary remission, and the patients almost inevitably develop hormone refractory prostate cancer (HRPC). HRPC is almost incurable, although most HRPC cells still express androgen receptor (AR) and depend on the AR for growth, making AR a prime drug target. Here, we provide evidence that epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is a direct antagonist of androgen action. In silico modeling and FRET-based competition assay showed that EGCG physically interacts with the ligand-binding domain of AR by replacing a high-affinity labeled ligand (IC(50) 0.4 μ M). The functional consequence of this interaction was a decrease in AR-mediated transcriptional activation, which was due to EGCG mediated inhibition of interdomain N-C termini interaction of AR. Treatment with EGCG also repressed the transcriptional activation by a hotspot mutant AR (T877A) expressed ectopically as well as the endogenous AR mutant. As the physiological consequence of AR antagonism, EGCG repressed R1881-induced PCa cell growth. In a xenograft model, EGCG was found to inhibit AR nuclear translocation and protein expression. We also observed a significant down-regulation of androgen-regulated miRNA-21 and up-regulation of a tumor suppressor, miRNA-330, in tumors of mice treated with EGCG. Taken together, we provide evidence that EGCG functionally antagonizes androgen action at multiple levels, resulting in inhibition of PCa growth.-Siddiqui, I. A., Asim, M., Hafeez, B. B., Adhami, V. M., Tarapore, R. S., Mukhtar, H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.
J Dermatol Sci. 2011 Jan;61(1):1-6. Epub 2010 Nov 3.
Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla.
Inui S, Itami S.
Department of Regenerative Dermatology, Osaka University School of Medicine, 2-2, G2, Yamadaoka, Suita-shi, Osaka 565-0871, Japan. firstname.lastname@example.org
Androgenetic alopecia (AGA) is characterized by vellus transformation of scalp hairs, corresponding to hair follicle miniaturization during repeated hair cycles with shortened anagen phase. This phenomenon is mediated mainly by androgen. Then, the multi-step molecular pathway of androgen can be involved in the pathogenesis of AGA. The expression of type II 5α-reductase is higher in dermal papilla cells from AGA and beard than those from other sites. On the other hand, type I 5α-reductase expression is relatively low. Next, hormone binding assays and RT-PCR demonstrated that androgen receptor (AR) expression is significantly higher in bald dermal papilla cells than non-bald cells. Additionally, AR coactivator Hic-5/ARA55 is highly expressed in dermal papilla cells of hair follicles from androgen-sensitive sites such as AGA and beard. Collectively, the enhanced expression of type II 5α-reductase, AR and Hic-5/ARA55 can upregulate sensitivity to androgen of dermal papilla cells in AGA. Furthermore, in the coculture of AR-overexpressing human dermal papilla cells from AGA and normal human keratinocytes, R1881 suppresses keratinocyte growth through androgen-inducible TGF-β1, indicating that TGF-β1 is one of the key players in pathogenesis of AGA. TGF-β2 and DKK-1 has been reported to be androgen-induced suppressor of growth of follicular epithelial cells. We expect that more pathogenic mediators will be identified in the future, enabling easier understanding of AGA pathogenesis and providing new therapeutic targets from aspect of andrology. Copyright Â© 2010 Japanese Society for Investigative Dermatology.
Exp Dermatol. 2010 Nov;19(11):1026-8. doi: 10.1111/j.1600-0625.2010.01132.x. Epub 2010 Sep 7.
Evidence for two independent functional variants for androgenetic alopecia around the androgen receptor gene.
Cobb JE, Zaloumis SG, Scurrah KJ, Harrap SB, Ellis JA.
Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia.
The gene encoding the androgen receptor (AR) is associated with male pattern baldness (androgenetic alopecia – AGA). In case-control and family analyses, we mapped AR and the adjacent intergenic regions. We found evidence for association with two independent loci, one upstream and previously described and the other downstream and apparently novel. The haplotype comprising these SNPs was strongly associated with AGA (P = 3.75 × 10(-5)) in 1195 men. We also replicated association with a recently reported non-coding region on chromosome 20 and found that its association with AGA was less strong and independent of that of AR. Our results will help focus future efforts to further define AGA genetic risk
Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen.
Ide H, Tokiwa S, Sakamaki K, Nishio K, Isotani S, Muto S, Hama T, Masuda H, Horie S.
Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.
BACKGROUND: Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. Since an elevated level of prostate-specific antigen (PSA) per se reflects the presence of inflammation in the prostate, intervention to improve the PSA value might potentially have beneficial effects for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti-inflammatory and anti-oxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP cells. After that, we conducted a clinical trial for men who received prostate biopsies, but were not found to have prostate cancer, to evaluate the effects of soy isoflavones and curcumin on serum PSA levels.
METHODS: The expression of androgen receptor and PSA were examined in LNCaP cells before and after treatment of isoflavones and/or curcumin. Eighty-five participants were randomized to take a supplement containing isoflavones and curcumin or placebo daily in a double-blind study. Subjects were subdivided by the cut-off of their baseline PSA value at 10 microg/ml. We evaluated values of PSA before and 6 months after treatment.
RESULTS: The production of PSA were markedly decreased by the combined treatment of isoflavones and curcumin in prostate cancer cell line, LNCaP. The expression of the androgen receptor was also suppressed by the treatment. In clinical trials, PSA levels decreased in the patients group with PSA >or= 10 treated with supplement containing isoflavones and curcumin (P = 0.01).
CONCLUSIONS: Our results indicated that isoflavones and curcumin could modulate serum PSA levels. Curcumin presumably synergizes with isoflavones to suppress PSA production in prostate cells through the anti-androgen effects.
Hong Kong Med J. 2001 Dec;7(4):369-74.
The medicinal action of androgens and green tea epigallocatechin gallate.
Tang Center for Herbal Medicine Research, Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois, USA.
Unorthodox (non-traditional or alternative) medicinal practices have been expanding very rapidly in western countries. Modern physicians, scientists, and non-traditional medicine practitioners now must join forces to promote evidence-based medicine to benefit patients. Green tea extracts are among the most widely used ancient medicinal agents, while androgens are probably the oldest drugs used in a purified form in traditional Chinese medicine. It is now clear that a specific green tea catechin, (-)epigallocatechin-3-gallate, can modulate the production and biological actions of androgens and other hormones. Modulation of androgenic activity and administration of (-)epigallocatechin-3-gallate may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, baldness, and acne, as well as androgen-dependent and -independent prostate cancers. (-)Epigallocatechin-3-gallate has also been shown to modulate appetite and control obesity in animals.