Methyl protogracillin (NSC-698792): the spectrum of cytotoxicity against 60 human cancer cell lines in the National Cancer Institute's anticancer drug screen panel

Methyl protogracillin (NSC-698792) was a furostanol saponin isolated from t he rhizome of Dioscorea collettii var, hypoglauca (Dioscoreaceae), a Chines e herbal remedy for the treatment of cervical carcinoma, carcinoma of urina ry bladder and venal tumor for centuries, in our previous studies. In order to systematically evaluate its potential anticancer activity, methyl proto gracillin was tested for Its cytotoxicity In vitro against 60 human cancer cell lines in the National Cancer Institute (NCI)'s anticancer drug screen. Pls a result, it was found that methyl protogracillin was cytotoxic agains t all the tested cell lines from leukemia and solid tumors in the NCI's hum an cancer panel; it showed particular selectivity against one colon cancer line (KM12), one central nervous system ((CNS) cancer line (U251), two mela noma lines (MALME-3M and M14), two renal cancer lines (786-0 and UO-31) and one breast cancer line (MDA-MB-231) with GI(50)less than or equal to2.0 mu M. The selectivity between these seven most sensitive lines and the least s ensitive line (CCRF-CEM) ranged from 26- to 56-fold. In the same cancer sub panel, selectivity more than 15-fold was observed between MDA-MB-231 and MC F-7, NCI-ADR-RES, BT-549 in breast cancer. From a general view of the mean graph, CNS cancer is the most sensitive subpanel, while ovarian cancer and renal cancer are the least sensitive subpanels. Based on an analysis of the COMPARE computer program with methyl protogracillin as a seed compound, no compounds in the NCI's anticancer drug screen database have similar cytoto xicity patterns (mean graph) to that of methyl protogracillin, indicating a potential novel mechanism of the anticancer action involved. [(C) 2001 Lip pincott Williams & Wilkins.].