APOPTOSIS AND CELL-CYCLE EFFECTS INDUCED BY EXTRACTS OF THE CHINESE HERBAL PREPARATION PC SPES

A herbal preparation denoted PC SPES(R) is available in 'natural food' or 'health food' stores in the United States. This mixture (patent pe nding, US Serial number 08/697,920) consists of extracts from 8 differ ent herbs, 7 originating from China and one from America, and is sold as a dietary supplement. Although several components of this herbal mi xture were reported to have antiproliferative and/or antitumor activit y little is known about the possible in vitro cytostatic or cytotoxic properties of the formulation. Composition of PC SPES is standardized by HPLC; the ethanol extract is characterized by the presence of 6 dis tinct components, reproducible from batch to batch. This extract suppr essed cell proliferation and reduced the clonogenicity of a variety of human tumor cell lines, including PC-3 and LNCaP prostate carcinomas, MCF-7 and T47-D breast carcinomas, SK-N-MC neuroepithelioma, Cole 38 melanoma, U937 histiomonocytic lymphoma, as well as HL-60 and MOLT-4 l eukemias. The sensitivity to PC SPES was different for particular cell lines, with MCF-7 cells being the most sensitive (IC50 = 20 nl/ml) an d Cole 38 the most resistant (IC50 = 430 nl/ml) in clonogenicity assay s. The predominant cell cycle effect induced by PC SPES was the prolon gation of G(1) phase. Apoptosis was observed after exposure of tumor c ells to PC SPES for 48 h and longer. PC SPES also downregulated expres sion of bcl-2, the gene protecting cells against apoptosis (studied in U937 cells) and sensitized these cells to gamma-irradiation. The cell cycle progression of mitogen stimulated human lymphocytes was not aff ected at PC SPES concentrations which induced cytotoxic and cytostatic effects in tumor cells. The data indicate that PC SPES is cytostatic and cytotoxic for different tumor cell lines and modulates the cell's propensity to undergo apoptosis.