Lappaconitine sulfate induces apoptosis and G0/G1 phase cell cycle arrest by PI3K/AKT signaling pathway in human non-small cell lung cancer A549 cells.

Lappaconitine sulfate (LS) has good solubility and bioavailability. We have previously studied the anti-proliferative activity of LS on colon cancer HT-29 cell, but its anti-proliferative activity and molecular mechanism on human non-small cell lung cancer A549 cells are still unclear. This study was to investigate the effects of LS on proliferation, cell cycle and apoptosis in human non-small cell lung cancer A549 cells, and its possible molecular mechanisms. Cell proliferation activity was measured by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) cell proliferation kit. Cell cycle was detected by propidium iodide (PI) flow cytometry. Apoptosis was detected by Annexin-V-FITC/PI method. Western blot was used to detect cycle and apoptosis-related proteins expression. These results showed that the proliferation activity of LS was significantly decreased in A549 cells, showing a dose- and time-dependent manner (p < 0.05). LS could increase the proportion of G0/G1 phase cells and decrease the proportion of cells in S phase, showing obvious G0/G1 phase arrest. LS significantly inhibited the expression of p-PI3K/PI3K, p-AKT/AKT, Cyclin D1 and Bcl-2 proteins (p < 0.05), and increased the expression of p53, p21, Bax, caspase 3 and caspase 9 (p < 0.05). Moreover, PI3K inhibitor (LY294002) significantly decreased A549 cell viability rate induced by LS, abrogated the activation of p-PI3K/PI3K and p-AKT/AKT in the presence of LS. These results indicated that LS could block A549 cells in the G0/G1 phase, induce apoptosis, and inhibit cell proliferation through the PI3K/AKT signaling pathway.