PC-SPES: A unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo

BACKGROUND. Management of prostate cancer that has spread beyond the capsul e is a difficult problem. Innovative and nontoxic approaches to the disease are urgently required. Recently, a commercially available herbal mixture c alled PC-SPES showed potent antitumor activities on a variety of malignant cells in vitro. METHODS. PC-SPES was evaluated for its ability to inhibit clonal growth, an d to induce cell cycle arrest of three human prostate cancer cell lines (LN CaP, PC-3, and DU 145). Western blot analysis examined the effect of PC-SPE S on levels of p21(waf1), p27(kip1), Bcl-2, and E-cadherin in the three cel l lines; and telomerase activity was examined by telomeric repeat amplifica tion protocol (TRAP) assay. Furthermore, the effect of oral PC-SPES (250 mg /kg/day) on growth of PC-3 and DU 145 tumors present in male BNX nu/nu trip le immunodeficient mice was studied. LNCaP cells were not analyzed in mice because they grow only with difficulty in these immunodeficient mice. RESULTS. PC-SPES markedly inhibited clonal growth of LNCaP, PC-3, and DU 14 5 prostate cancer cells, with a 50% inhibition (ED50) at approximately 2 mu l/ml. Pulse-exposure studies showed that a Ei-day pulse-exposure to PC-SPE S (2 mu l/ml) in liquid culture achieved a 50% inhibition of PC-3 clonal gr owth in soft agar, suggesting that the growth inhibition mediated by the ex tracts remained after removal of PC-SPES. Cell cycle analysis using the pro state cancer cell lines found that PC-SPES induced a significant increase i n the number of cells in G0-G1 and G2/M, with a concomitant decrease in the number of cells in S phase. PC-SPES (2 mu l/ml, 4 days) increased slightly the levels of p21(waf1) in the three cell lines, decreased by 40% the leve ls of Bcl-2 in PC-3, and the levels of p27(kip1) and E-cadherin and telomer ase were unchanged in each of the lines. In vivo treatment with oral PC-SPE S of male BNX mice having DU 145 tumors produced significant inhibition of their growth (P < 0.001), with no objective side effects including blood ch emistries, weights, or autopsy analysis. The PC-SPES showed no statistical effect on the in vivo growth of PC-3 cells. CONCLUSIONS. PC-SPES inhibits clonal proliferation of human prostate cancer cells both in vitro and in vi iio, using a murine model.