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

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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. (JNCI 17: 1275 (2002)) concluded that the contaminants were responsible for cytotoxicity of this preparation. We have shown 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 (Sadava et al., Cancer Chemo. Pharmacol. 49: 261 (2002)) and investigated whether the contaminants might be responsible for these effects. In contrast to the data reported for prostate carcinoma cells, extracts of lots of PC-SPES from 1998 (reportedly contaminated) and 2001 (much less contaminated) were equally cytotoxic in both SCLC cell lines. Tests of individual contaminants gave IC₅₀ values far in excess of the amounts reported to be present in the IC₅₀ level for the PC-SPES extracts: Diethlystilbesterol: actual IC₅₀ in H69 cells, > 1000 uM; concentration present in herbal extract at IC₅₀, 0.05-0.2 uM; indomethacin: actual IC₅₀ in H69 cells, 800 uM; concentration in herbal extract, 1.5-20 uM; warfarin: actual IC₅₀ in H69 cells, 950 uM; concentration in herbal extract, 0.57-0.93 uM. Adding the calculated maximum concentration of the contaminants, singly or in combination, to extracts of the later (2001) batch of PC-SPES did not alter the cytotoxicity of the extract in H69 or H69V cells. At the contaminated concentrations, as well as 5x 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 H69 and H69V cells. We conclude that the traces of pharmaceuticals found in PC-SPES were not responsible for its cytotoxic and pro-apoptotic activities on SCLC cells.