7-脱氧水仙环素的分离纯化及其体外抗肿瘤活性研究

Isolation and Purification of 7-deoxynarciclasine and Its Antitumor Activity in Vitro

摘要:

本研究对石蒜属植物石蒜的活性部位正丁醇部位进行分级纯化得到一个化合物，对该化合物进行质谱及核磁共振波谱分析，鉴定该化合物为7-脱氧水仙环素。研究7-脱氧水仙环素对人体正常细胞(LO2细胞和HFF-1细胞)的细胞毒性及对人宫颈癌细胞（Hela细胞）和人结肠癌细胞（HT-29细胞）的细胞存活率的影响。结果显示人包皮成纤维细胞（HFF-1细胞）对7-脱氧水仙环素的耐受性要大于人正常肝细胞（LO2细胞）。选择使LO2细胞存活率高于80%的7-脱氧水仙环素浓度作用于肿瘤细胞HT-29和Hela。结果显示7-脱氧水仙环素对HT-29和Hela的半数致死浓度（IC50）分别为17.04 μM和6.39 μM，低于5-氟尿嘧啶的22.45 μM和37.05 μM，且低于7-脱氧水仙环素对LO2细胞的半数致死浓度（IC50）40.11 μM，说明7-脱氧水仙环素在对正常细胞无明显影响的情况下能显著抑制肿瘤细胞的增值。

Abstract:

In this study, a compound was obtained from the n-butanol fraction of the active part of Lycoris radiate Herb. The compound was identified as 7-deoxynarciclasine by mass spectrometry and Nuclear Magnetic Resonance spectroscopy. To study the cytotoxicity of 7-deoxynarciclasine against normal human cells (LO2 cells and HFF-1 cells), and its effect on the cell viability of human cervical cancer cells (Hela cells) and human colon cancer cells (HT-29 cells) were examined. The results showed that human foreskin fibroblasts (HFF-1 cells) were more tolerant to 7-deoxynarciclasine than normal human hepatocytes (LO2 cells). The concentration of 7-deoxycycline, which led to a LO2 cell survival rate higher than 80%, was applied to HT-29 and Hela cells. As a result, the median lethal concentration (IC50) of 7-deoxynarciclasine to HT-29 or Hela cells was 17.04 μM and 6.39 μM respectively. These values were lower than those of 5- fluorouracil against HT-29 (22.45 μM) or Hela cells (37.05 μM), and that against LO2 (40.11 μM). These findings indicate that 7-deoxynarciclasine may significantly inhibit the proliferation of tumor cells without affecting significantly the normal cells.