Contaminants of PC-SPES are not responsible for cytotoxicity in human small-cell lung carcinoma cells

Abstract

PC-SPES is a mixture of herbs used in the treatment of prostate cancer. Batches of this product were found to contain traces of synthetic drugs, and the product was removed from the market. On the basis of a correlation between contaminant levels and cytotoxicity in prostate carcinoma cell lines, Sovak et al. [M. Sovak, A. Seligson, M. Konas, M. Hajduch, M. Dolezal, M. Machala, R. Nagourney, Herbal composition PC-SPES for management of prostate cancer: identification of active principles, J. Natl Cancer Inst. 94 (2002) 1275–1281] concluded that the contaminants were responsible for cytotoxicity of this preparation. Previously, we showed that extracts of PC-SPES are cytotoxic and pro-apoptotic in both drug-sensitive (H69) and drug resistant (H69V) human small-cell lung carcinoma (SCLC) cell lines. Here, we investigated whether the contaminants might be responsible for these effects. In contrast to the data reported for prostate carcinoma cells, extracts of batches of PC-SPES from the year 1998 (reportedly contaminated) and 2001 (much less contaminated) were equally cytotoxic in both SCLC cell lines. Tests of individual contaminants gave IC 50 values far in excess of the amounts reported to be present in the IC 50 level for the PC-SPES extracts: diethlystilbesterol: actual IC 50 in H69 cells, >1000 μM; concentration present in herbal extract at IC 50, 0.05–0.2 μM; indomethacin: actual IC 50 in H69 cells, 800 μM; concentration in herbal extract, 1.5–20 μM; warfarin: actual IC 50 in H69 cells, 950 μM; concentration in herbal extract, 0.57–0.93 μM. Adding the calculated maximum concentration of the contaminants, singly or in combination, to extracts of the less contaminated batch (2001) of PC-SPES did not alter the cytotoxicity of the extract in H69 or H69V cells. At the contaminated concentrations, as well as 5× those concentrations, none of the contaminants was pro-apoptotic, as indicated by a DNA fragmentation kinetics assay. However, extracts of both early and late batches of PC-SPES were pro-apoptotic in SCLC cells. We conclude that the traces of pharmaceuticals found in PC-SPES were not responsible for its cytotoxic and pro-apoptotic activities of this herbal mixture on SCLC cells.