Abstract:
:Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for PCa and has serious toxic sideeffects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of PCa. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakai (Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5alpha-dihydrotestesterone to AR and increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the "pure" anti-androgen bicalutamide and is more potent than bicalutamide in inducing PCa apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomer decursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-androgen/ AR agents from complex herbal mixtures.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Lu J,Kim SH,Jiang C,Lee H,Guo Jdoi
10.1111/j.1745-7254.2007.00683.xsubject
Has Abstractpub_date
2007-09-01 00:00:00pages
1365-72issue
9eissn
1671-4083issn
1745-7254journal_volume
28pub_type
杂志文章,评审abstract::As autophagy is involved in cell growth, survival, development and death, impaired autophagic flux has been linked to a variety of human pathophysiological processes, including neurodegeneration, cancer, myopathy, cardiovascular and immune-mediated disorders. There is a growing need to identify and quantify the status...
journal_title:Acta pharmacologica Sinica
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abstract:AIM:To investigate the prevalence of hepatitis B virus (HBV) genotype mixtures among patients with chronic hepatitis B (CHB) in Eastern China. METHODS:A total of 4908 chronic HBV patients from Eastern China were enrolled. HBV genotypes and subgenotypes were determined using a multiplex PCR technique. Serum viral loads...
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更新日期:2013-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-10-01 00:00:00
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更新日期:2004-06-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2017-05-01 00:00:00