Hu K, Yao X S
Department of Pharmaceutical Sciences, School of Pharmacy, State University of New York at Buffalo, 14260, USA.
Anticancer Res. 2002 Mar-Apr;22(2A):1001-5.
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.
甲基原薯蓣皂苷（NSC - 698791）是一种呋甾烷醇皂苷，从粉背薯蓣（薯蓣科）的根茎中分离得到，数个世纪以来，该植物一直作为治疗宫颈癌、膀胱癌和肾肿瘤的一种中草药。为了系统地评估其潜在的抗癌活性，在美国国立癌症研究所（NCI）的抗癌药物筛选中，对甲基原薯蓣皂苷的细胞毒性进行了体外测试，针对60种人类癌细胞系。结果显示，甲基原薯蓣皂苷对NCI人类癌症细胞库中所有白血病和实体瘤测试细胞系均具有细胞毒性，尤其对一种非小细胞肺癌（NSCLC）细胞系（A549/ATCC）、一种结肠癌细胞系（HCT - 116）、两种中枢神经系统（CNS）癌细胞系（SF - 539和SNB - 75）、一种黑色素瘤细胞系（M14）、一种肾癌细胞系（CAKI - 1）、一种前列腺癌细胞系（DU - 145）以及两种乳腺癌细胞系（HS 578T和MDA - MB - 435）具有选择性细胞毒性，其半数生长抑制浓度（GI50）≤2.0微摩尔。这9种最敏感细胞系与最不敏感细胞系（TK - 10）之间的选择性为22至30倍。在同一癌症亚组中，在A549/ATCC与EKVX（NSCLC）之间、CAKI - 1与TK - 10、A498（肾癌细胞系）之间，在GI50水平观察到超过15倍的选择性。总体而言，中枢神经系统癌症是最敏感的亚组，而肾癌是最不敏感的亚组。基于以甲基原薯蓣皂苷为种子化合物对COMPARE计算机程序的分析，NCI抗癌药物筛选数据库中没有化合物具有与甲基原薯蓣皂苷相似的细胞毒性模式（平均图谱），这表明其涉及一种潜在的新型抗癌作用机制。
