Activity of camptothecin, harringtonin, cantharidin and curcumae in the human tumor stem cell assay.
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Abstract
The antitumor activity of four investigational natural products (camptothecin, harringtonin, cantharidin and curcumae) obtained from China were tested on human tumor biopsies in an in vitro soft agar clonogenic assay system. Significant antitumor activity was seen with camptothecin against human ovarian cancer and some other adenocarcinomas. Antitumor activity was also observed for harringtonin against adenocarcinoma and sarcoma. Both drugs also appeared to show activity in melanoma and mesothelioma. However, cantharidin and curcumae were relatively ineffective on the human tumors tested. For purposes of comparing the intensity of antitumor effects with standard cytotoxic drugs to those of the four new agents, the ID50 values were calculated. The ratio of ID50S of new drugs to the standard agents doxorubicin, cis-platinum and vinblastine (ID50 of the standard drug/ID50 of tested drug) were 10.2, 64.1 and 1.9 for camptothecin and 1.5, 10.3 and 0.9 for harrington respectively. A relationship was observed between the duration of drug exposure (1 hr prior to plating vs continuous contact in the agar) and inhibition of clonogenic tumor cells for camptothecin, harringtonin and doxorubicin.