Characterization of Chemical Constituents in Scutellaria baicalensis with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma Export

@article{citeulike:1984146, abstract = {Purpose: Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action. Experimental Design and Results: We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r2 = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55\% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of [\~{}]1,000 mm3 from 16 to 47 days (P < 0.001). Conclusions: Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted. 10.1158/1078-0432.CCR-04-1974}, author = {Bonham, Michael and Posakony, Jeff and Coleman, Ilsa and Montgomery, Bruce and Simon, Julian and Nelson, Peter S.}, citeulike-article-id = {1984146}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-04-1974}, citeulike-linkout-1 = {http://clincancerres.aacrjournals.org/cgi/content/abstract/11/10/3905}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15897592}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15897592}, day = {15}, doi = {10.1158/1078-0432.CCR-04-1974}, journal = {Clin Cancer Res}, keywords = {active-constituents, androgen-inhibitors, androgens, antiandrogenic, baicalensis, botanical-medicine, carcinoma, constituents, free, full-text, fulltext, herbal-medicine, herbs, inhibitors, pdf, phytochemicals, phytomedicine, preclinical, prostate, prostate-cancer, prostate-carcinoma, research, scutellaria, scutellaria-baicalensis}, month = {May}, number = {10}, pages = {3905--3914}, posted-at = {2007-11-26 08:42:01}, priority = {5}, title = {Characterization of Chemical Constituents in Scutellaria baicalensis with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-04-1974}, volume = {11}, year = {2005} }

TY - JOUR ID - citeulike:1984146 L3 - citeulike-article-id:1984146 N2 - Purpose: Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action. Experimental Design and Results: We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r2 = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of [~]1,000 mm3 from 16 to 47 days (P < 0.001). Conclusions: Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted. 10.1158/1078-0432.CCR-04-1974 IS - 10 JF - Clin Cancer Res EP - 3914 TI - Characterization of Chemical Constituents in Scutellaria baicalensis with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma VL - 11 SP - 3905 KW - active-constituents KW - androgen-inhibitors KW - androgens KW - antiandrogenic KW - baicalensis KW - botanical-medicine KW - carcinoma KW - constituents KW - free KW - full-text KW - fulltext KW - herbal-medicine KW - herbs KW - inhibitors KW - pdf KW - phytochemicals KW - phytomedicine KW - preclinical KW - prostate KW - prostate-cancer KW - prostate-carcinoma KW - research KW - scutellaria KW - scutellaria-baicalensis AU - Bonham, Michael AU - Posakony, Jeff AU - Coleman, Ilsa AU - Montgomery, Bruce AU - Simon, Julian AU - Nelson, Peter PY - 2005/05/15/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-04-1974 ER -