Lappaconitine sulfate induces apoptosis in human colon cancer HT-29 cells and down-regulates PI3K/AKT/GSK3β signaling pathway.

Lappaconitine (LA), a diterpenoid alkaloid extracted from the roots of Aconitum sinomontanum Nakai, possesses strong central analgesic, local anesthetic, antifebric and anti-inflflammatory effect. Lappaconitine hydrobromide (LH) is used clinically to treat analgesia, but its clinical application is limited because of its poor solubility in water. Studies have suggested that lappaconitine sulfate (LS) is a promising pain reliever, and this particular form not only has readily water soluble, but also exhibits anti-cancer effects. However, the mechanism of LS anti-cancer activity is poorly understood. The aim of this study was intended to investigate the role of LS in apoptosis of human colon cancer HT-29 cells and explore the potential molecular mechanism. Cell proliferation was detected by CCK-8 assay and EdU proliferation assay. Cell morphological change was expressed by Hoechst 33258 staining assay. Expression of apoptosis related proteins were detected by western blot. The effect of LS on cell cycle was detected by flow cytometry. Experimental results showed that LS exhibited anti-proliferative activity and induced apoptosis in HT-29 cells in a dose-dependent manner. LS increased the expression of p53, Bax, cleaved-PARP, cleaved-caspase-3/7/9, and inhibited Bcl-2 expression. LS affected cyclin D1 and p21 expression and induced cell cycle arrest in G0/G1 phase. Additionally, LY294002 signifificantly abrogated the activation of p-PI3K, p-Akt and p-GSK3β. To summarize, these results demonstrated that LS was able to prevent cell proliferation probably via PI3K/Akt/GSK3β signaling pathway. [ABSTRACT FROM AUTHOR]