Sadava David, Winesburg Jennifer
Keck Science Center, 925 N. Mills Ave., Claremont, CA 91711, USA.
Cancer Lett. 2005 Apr 8;220(2):171-5. doi: 10.1016/j.canlet.2004.09.010.
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 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 microM; concentration present in herbal extract at IC50, 0.05-0.2 microM; indomethacin: actual IC50 in H69 cells, 800 microM; concentration in herbal extract, 1.5-20 microM; warfarin: actual IC50 in H69 cells, 950 microM; concentration in herbal extract, 0.57-0.93 microM. 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 x 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.
PC-SPES是一种用于治疗前列腺癌的草药混合物。人们发现该产品批次中含有痕量合成药物，于是该产品被撤出市场。基于前列腺癌细胞系中污染物水平与细胞毒性之间的相关性，索瓦克等人[M. 索瓦克、A. 塞利格森、M. 科纳斯、M. 哈伊杜赫、M. 多莱扎尔、M. 马沙拉、R. 纳古尔内，用于治疗前列腺癌的草药组合物PC-SPES：活性成分鉴定，《美国国家癌症研究所杂志》94 (2002) 1275 - 1281]得出结论，污染物是该制剂细胞毒性的原因。此前，我们表明PC-SPES提取物对药物敏感（H69）和耐药（H69V）的人小细胞肺癌（SCLC）细胞系均具有细胞毒性和促凋亡作用。在此，我们研究了污染物是否可能是这些作用的原因。与前列腺癌细胞的报道数据相反，1998年（据报道有污染）和2001年（污染程度低得多）批次的PC-SPES提取物在两种SCLC细胞系中的细胞毒性相同。对单个污染物的测试得出的半数抑制浓度（IC50）值远远超过PC-SPES提取物IC50水平所报道的存在量：己烯雌酚：在H69细胞中的实际IC50，>1000微摩尔；在IC50时草药提取物中的浓度，0.05 - 0.2微摩尔；吲哚美辛：在H69细胞中的实际IC50，800微摩尔；在草药提取物中的浓度，1.5 - 20微摩尔；华法林：在H69细胞中的实际IC50，950微摩尔；在草药提取物中的浓度，0.57 - 0.93微摩尔。将计算出的污染物最大浓度单独或组合添加到污染程度较低的2001年批次PC-SPES提取物中，并未改变提取物对H69或H69V细胞的细胞毒性。在污染浓度以及5倍该浓度下，通过DNA片段化动力学分析表明，没有一种污染物具有促凋亡作用。然而，早期和晚期批次的PC-SPES提取物在SCLC细胞中均具有促凋亡作用。我们得出结论，PC-SPES中发现的痕量药物并非该草药混合物对SCLC细胞的细胞毒性和促凋亡活性的原因。
