Hederacolchiside A1 suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K/Akt/mTOR signaling pathway / 中草药·英文版

ABSTRACT

Objective: Hederacolchiside A1, exhibits cytostatic and cytotoxic activity against various cancer cells in vitro, however, the mechanism is not well understood. Methods: 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. Results: 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. Conclusion: These data indicated that hederacolchiside A1 suppressed the proliferation of human tumor cells by inducing apoptosis through modulating the PI3K/Akt/mTOR signaling pathway.