海南地不容生物碱抑制肿瘤细胞增殖及构效关系解析

Study on Inhibition of Tumor Cell Proliferation and Analysis on Structure-Activity Relationship of Stephania hainanensis H.S.Lo et Y.Tsoong Alkaloids

目的研究海南地不容(Stephania hainanensis H.S.Lo et Y.Tsoong)生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的影响,筛选出有效的抗肿瘤化合物以及其敏感细胞株;分析其生物碱的构效关系。方法采用MTT法检测不同浓度的海南地不容生物碱对人肝癌细胞Hep G-2、乳腺癌细胞MCF-7、胃癌细胞SGC-7901增殖的抑制率;通过查阅国内外相关文献,分析海南地不容生物碱抗肿瘤活性的基本构效关系。结果MTT结果显示荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁对人肝癌Hep G-2、乳腺癌MCF-7和胃癌SGC-7901细胞的增值分别具有不同程度的剂量依赖性的抑制作用,各给药组分吸光度值与空白对照组比具有显著性差异(P<0.01),与阳性对照比较无明显统计学差异(P>0.05);海南地不容生物碱结构中的1,2-亚甲二氧基、N-亚甲基等取代基以及其化学结构的平面性对其抗肿瘤活性有重要影响。结论海南地不容中具有明显抗肿瘤作用的生物碱为荷包牡丹碱、氧化克班宁、去甲荷包牡丹碱和克班宁,其敏感细胞株均为乳腺癌细胞MCF-7;通过分析海南地不容生物碱的结构和抗肿瘤活性的关系,初步明确了其抗肿瘤活性可能与其结构易于抑制DNA拓扑异构酶和诱导细胞凋亡有关。

Objective To study the proliferating effects of Stephania hainanensis H.S.Lo et Y.Tsoong alkaloids against the hepatoma cells HepG-2,breast cancer cells MCF-7 and gastric cancer cells SGC-7901 and screen out the effective anti-tumor compounds and their sensitive cells.To analyze the structure-activity relationship of alkaloids.Methods The proliferating inhibition of the different concentrations of Stephania hainanensis H.S.Lo et Y.Tsoong alkaloids against human hepatoma cells HepG-2,breast cancer cells MCF-7 and gastric cancer cells SGC-7901 was analyzed by MTT assays.The relevant literature at home and abroad was reviewed to analyze the basic structure-activity relationship of anti-tumor activity of Stephania hainanensis H.S.Lo et Y alkaloids.Results MTT test results showed that Dicentrine,Oxocrebanine,Demethydicentrine and Crebanine had different dose-dependent effects and can inhibit hepatoma cancer HepG-2,breast cancer MCF-7 and gastric cancer SGC-7901 cells.The OD values of each drug component were decreased compared with those of the blank control group(P<0.01),and there was no difference between the fractions and positive group(P>0.05)in the MTT experiment.There was an important influence on antitumor activity of the substitution of 1,2-methylenedioxy,N-methylene and other substituents in the alkaloids structure of Stephania hainanensis H.S.Lo et Y.Conclusion The compounds with obvious anti-tumor effect of Stephania hainanensis H.S.Lo et Y are Dicentrine,Oxocrebanine,Demethydicentrine and Crebanine.The sensitive cell lines are breast cancer cells MCF-7.The relationship was analyzed between the structure and the anti-tumor activities of Stephania hainanensis H.S.Lo et Y alkaloids.It is preliminarily confirmed that the anti-tumor activity may be related to its structure easily inhibiting DNA topoisomerase and inducing apoptosis.