title: The cytotoxicity of methyl protoneodioscin (NSC-698791) against human cancer cell lines in vitro.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, State University of New York at Buffalo, 14260, USA. kehu@acsu.buffalo.edu
authors.forename: K
authors.initials: K
authors.lastname: Hu
authors.forename: X S
authors.initials: XS
authors.lastname: Yao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D027742:Dioscorea / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D014315:Triterpenes; C457767:methyl protoneodioscin