Effects of the herbal extract PC-SPES on microtubule dynamics and paclitaxel-mediated prostate tumor growth inhibition

Background: PC-SPES is a botanical preparation shown to have efficacy in patients with androgen-dependent and androgen-independent prostate carcinoma. Several herbal constituents in PC-SPES inhibit tumor growth through cell cycle arrest and apoptosis, although the mechanisms of these activities are poorly defined. We sought to identify PC-SPES-induced changes in gene expression, specifically in those genes encoding cytoskeletal proteins that could be as-sociated with PC-SPES-induced cytoxicity. Methods: LNCaP prostate carcinoma cells were treated with PC-SPES, and changes in gene expression were determined by complemen-tary DNA (cDNA) microarray hybridization and northern blot analyses. PC-SPES and paclitaxel, a microtubule-stabilizing drug, effects on microtubules were assessed by immunofluorescence of treated cells and by in vitro tubulin polymerization assays. In vivo effects of PC-SPES and pacli-taxel were assessed using CWR22R androgen-independent prostate cancer xenografts. All statistical tests were two-sided. Results: PC-SPES treatment of LNCaP cells for 24 hours altered the expression of 17 cytoskeletal genes. mRNA levels of -tubulin decreased sevenfold. Although paclitaxel stabilized and PC-SPES treatment disrupted microtubule architecture in LNCaP cells, the combination of both agents had an intermediate effect. PC-SPES inhibited tubulin po-lymerization in vitro, even in the presence of paclitaxel. Com-pared with tumors in control mice (mean tumor volume = 2983 mm3, 95 % confidence interval [CI] = 2380 to 3586 mm3), tumors were statistically significantly smaller in mice that received PC-SPES (mean tumor volume = 2018 mm3