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CPUK02(15-羰基甜菊苷苄酯)是由甜菊苷半合成得到的一种新型化合物。采用多种体内体外模型验证了其抗肿瘤活性, 并初步探索了其抗肿瘤活性的作用机理。使用MTT法测试了该化合物的体外抗肿瘤活性, 发现CPUK02对于多种肿瘤细胞株都有显著地抑制作用; 此外, 对于肝癌细胞该化合物的作用相较于正常肝细胞有着显著地敏感性差异, 尤其在低浓度下,该化合物对癌细胞表现出较强的选择性。在多种人癌细胞小鼠异种移植瘤模型中, CPUK02表现出接近五氟尿嘧啶的抗肿瘤活性。同时使用Annexin/PI双染流式细胞术和DAPI染色的方法观察了CPUK02引起的肿瘤细胞的细胞形态学上的变化, 证明了该化合物确实可以诱导细胞凋亡, 该作用同时表现出明显的浓度依赖性。还使用了western blot探索了该化合物的抗肿瘤作用的机理, 发现该化合物可以作用于细胞凋亡的线粒体途径激活凋亡信号的级联转导。这些结果显示CPUK02是一种良好的抗肿瘤候选化合物, 并且有可能成为一种有前途的新型药物。
CPUK02 (15-carbonyl stevioside benzyl ester) is a novel compound obtained from the semi-synthesis of stevioside. The anti-tumor activity was verified by a variety of in vitro and in vivo models and the mechanism of anti-tumor activity was initially explored. The antitumor activity of this compound was tested by MTT assay. It was found that CPUK02 had a significant inhibitory effect on many tumor cell lines. In addition, the effect of this compound on hepatoma cells was significantly different from that of normal hepatocytes. Especially at low concentrations, the compounds show a strong selectivity for cancer cells. In a variety of human cancer cell xenograft models, CPUK02 showed nearly antitumor activity against pentafluorouracil. At the same time, the morphological changes of tumor cells induced by CPUK02 were observed by using Annexin / PI double staining flow cytometry and DAPI staining, and it was proved that the compound could indeed induce apoptosis, and the effect showed obvious concentration Dependency. A western blot was also used to explore the antitumor mechanism of this compound and found that the compound acts on the cascade of apoptotic mitochondrial pathway activation of apoptotic signals. These results show that CPUK02 is a good anti-tumor candidate compound, and may become a promising new drug.