Methyl protoneodioscin (NSC-698791) is a furostanol
saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical
carcinoma,
carcinoma of the urinary bladder and renal
tumor for centuries. In order to systematically evaluate its potential anticancer activity,
methyl protoneodioscin cytotoxicity was tested in vitro against 60 human
cancer cell lines in the NCI's (National Cancer Institute, USA) anticancer
drug screen. As a result,
methyl protoneodioscin was cytotoxic against all the test cell lines from
leukemia and solid
tumors in the NCI's human
cancer panel, especially selectively against one
non-small cell lung cancer (NSCLC) line (A549/ATCC), one
colon cancer line (HCT-116), two central nenous system (CNS)
cancer lines (SF-539 and SNB-75), one
melanoma line (M14), one
renal cancer line (CAKI-1), one
prostate cancer (DU-145) and two
breast cancer lines (HS 578T and MDA-MB-435) with GI50 < or = 2.0 microM. The selectivity between these nine most sensitive lines and the least sensitive line (TK-10) was from 22- to 30- fold. In the same
cancer subpanel, a selectivity at GI50 level of more than 15-fold was observed between A549/ATCC and EKVX (NSCLC), between CAKI-1 and TK-10, A498 (
renal cancer), respectively. In general the CNS
cancer was the most sensitive subpanel, while
renal cancer was the least sensitive subpanel. Based on an analysis of COMPARE computer program with
methyl protoneodioscin as a seed compound, no compounds in the NCIs anticancer
drug screen database have similar cytotoxicity patterns (mean graphs) to that of
methyl protoneodioscin, indicating a potential novel mechanism of anticancer action involved.