Hederacolchiside A1, exhibits cytostatic and cytotoxic activity against various cancer cells in vitro, however, the mechanism is not well understood. In this study, Hederacolchiside A1 from Pulsatilla chinensis was isolated and tested its anticancer activity and mechanism. Hederacolchiside A1 could inhibit proliferation of A549, SMMC-7721, BEL-7402, and MCF-7 cells by MTT assay. Investigations of apoptosis of treated cancer cells were identified in hederacolchiside A1 by flow cytometric analysis of annexin V expression. Based on the results of western blotting and JC-1 staining, hederacolchiside A1 reduced the mitochondrial membrane potential and Bcl-2 protein levels, whereas cleaved caspase-3 was higher. Furthermore, hederacolchiside A1 effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). In vivo study showed that hederacolchiside A1 (3.0, 4.5, and 6.0 mg/kg, ip) could significantly inhibit the weight of tumor in an H22 xenograft model. Similar inhibitory activities were observed when the compound (3.25, 7.5, and 15.0 mg/kg, ig) was tested in nude mice xenograft tumor models using human breast carcinoma MCF-7 cells. These data indicated that hederacolchiside A1 suppressed the proliferation of human tumor cells by inducing apoptosis through modulating the PI3K/Akt/mTOR signaling pathway.
关键词:
细胞凋亡; Hederacolchiside A1; 线粒体途径;PI3K-Akt-mTOR途径
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This paper was funded by the National Sciences Foundation of China (No.81273402, 81573548).
