| PC-SPES is a complex mixture of 8 Chinese herbs developed as an alternative treatment for prostate cancer. Clinical trials studying PC-SPES demonstrated substantial responses in patients with advanced prostate cancer. Biochemical assays and clinical observations suggest that PC-SPES effects are mediated at least in part through estrogenic activity, although the mechanism(s) and active compounds remain largely undefined.; DNA microarray analysis of LNCaP cells exposed to PC-SPES identified regulation of cell cycle and androgen responsive genes by the extract. A comparison of gene expression profiles indicated PC-SPES exhibited activities distinct from those attributable to DES and estradiol. Also, PC-SPES decreased alpha/beta tubulin expression, disrupted the microtubule architecture of prostate carcinoma cells and directly inhibited glutamate/GTP-induced assembly of purified tubulin monomers. While PC-SPES and the microtubule-stabilizing drug paclitaxel each individually inhibited growth in cell culture and a xenograft mouse model, concurrent treatment with these agents produced an antagonistic effect.; A screen of Scutellaria baicalensis, one of herbs in PC-SPES, isolated and identified four growth inhibitory compounds: baicalein, wogonin, neobaicalein, and skullcapflavone. DNA microarray analysis of LNCaP cells treated with the 4 compounds at their respective IC50 concentration did not show distinctive differences in gene expression alterations. As with PC-SPES, changes in genes transcriptionally regulated by the androgen receptor and controlling the cell cycle/cell growth were consistently altered. LC-MS analysis determined the 4 compounds are major components of the ethanolic extract comprising 10% of the extract's dry weight. Next, the 4 compounds were combined at concentrations found in the Scutellaria baicalensis extract. This combination caused a similar level of growth inhibition and gene expression alterations as the entire extract, suggesting the four compounds are the only active components of the extract.; In conclusion, four growth inhibitory compounds from PC-SPES were identified. The compounds can both inhibit tumor cell growth and decrease AR transcriptional activity, suggesting they contribute to the beneficial effects observed clinically with PC-SPES. Future studies to determine the molecular targets of the compounds, mechanisms of growth inhibition and whether the compounds could be effective as stand alone agents in the prevention or treatment of prostate cancer are warranted. |
