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Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents

Acta Pharmacologica Sinica 2007年第9期28卷 1365-1372页

作者： HyoJeong LEE Hormel Institute University of MinnesotaAustinMN 55912USA College of Oriental MedicineKyunghee UniversitySeoul 131-701Korea

androgen and androgen receptor (AR) signaling are crucial for the genesis ofprostate cancer (PCa),which can often develop into androgen-ligand-indepen-dent diseases that are lethal to the *** studies show that even thesehormone-refractory PCa require ligand-independent AR signaling for *** chemotherapy is largely ineffective for PCa and has serious toxic side-effects,we have initiated a collaborative effort to identify and develop novel,safeand naturally occurring agents that target AR signaling from Oriental medicinalherbs for the chemoprevention and treatment of *** highlight our discoveryof decursin from an Oriental formula containing Korean Angelica gigas Nakai(Dang Gui) root as a novel anti-androgen/AR *** have identified thefollowing mechanisms to account for the specific anti-AR actions:rapid block ofAR nuclear translocation,inhibition of binding of 5α-dihydrotestesterone to ARand increased proteasomal degradation of AR ***,decursinlacks the agonist activity of the"pure"anti-androgen bicalutamide and is morepotent than bicalutamide in inducing PCa ***-activity analysesreveal a critical requirement of the side-chain on decursin or its structural isomerdecursinol angelate for anti-AR,cell cycle arrest and proapoptotic *** demonstrates the feasibility of using activity-guided fractionation in cellculture assays combined with mechanistic studies to identify novel anti-andro-gen/AR agents from complex herbal mixtures.

关键词： anti-androgen prostate cancer chemoprevention pyranocoumarin herbal medicine

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The effect of flutamide on the physical working capacity and activity of some of the key enzymes for the energy supply in adult rats

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Asian Journal of Andrology 2017年第4期19卷 444-448页

作者： Katerina N Georgieva Penka A Angelova Fani D Gerginska Dora D Terzieva Mihaela S Shishmanova-Doseva Slavi D Delchev Valentine V Vasilev Department of Physiology Faculty of Medicine Medical University of Plovdiv Plovdiv 4000 Bulgaria Department of Anatomy Histology and Embryology Faculty of Medicine Medical University of Plovdiv Plovdiv 4000 Bulgaria Department of Clinical Chemistry Faculty of Pharmacy Medical University of Plovdiv Plovdiv 4000 Bulgaria Department of Pharmacology and Drug Toxicology Faculty of Pharmacy Medical University of Plovdiv Plovdiv 4000 Bulgaria

The aim of the study was to assess the effects of androgen receptor antagonists on the physical working capacity and activity of some of the key muscle enzymes for the energy supply in rats. Young adult male Wistar rats were divided into two groups. One group received 15 mg kg-1 of flutamide daily for 6 days a week and the other group served as control for 8 weeks. At the beginning and at the end of the experiment, all rats were subjected to submaximal running endurance （SRE）, maximum time to exhaustion （MTE）, and maximal sprinting speed （MSS） tests. At the end of the trial, maximum oxygen consumption （VO2max） test was performed and the levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of succinate dehydrogenase （SDH）, lactate dehydrogenase （LDH）, and NAD.H2-cytochrome-c reductase （NAD.H2） of the gastrocnemius muscle were measured. Serum testosterone of the flutamide-treated rats was higher than that of the controls, which verifies the effectiveness of the dose chosen. MTE and SRE of the anti-androgen-treated group were lower compared with the initial values. Flutamide treatment decreased the activity of SDH and NAD.H2 compared with the controls. We found no effect of the anti-androgen treatment on MSS, VO2max, running economy, LDH activity, and hematological variables. Our findings indicate that the maintenance of the submaximal and maximal running endurance as well as the activity of some of the key enzymes associated with muscle oxidative capacity is connected with androgen effects mediated by androgen receptors.

关键词： anti-androgen maximum oxygen consumption maximum time to exhaustion mitochondrial enzymes running economy submaximal running endurance

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Use of androgen deprivation therapy in prostate cancer： indications and prevalence

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Asian Journal of Andrology 2012年第2期14卷 177-186页

作者： Roisin M Connolly Michael A Carducci Emmanuel S Antonarakis Prostate Cancer Research Program Department of Medical Oncology Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD 21231-1000 USA

androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

关键词： androgen deprivation therapy androgen synthesis anti-androgen prostate cancer

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