aconitine and Lung-Neoplasms

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.

Topics: A549 Cells; Aconitine; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; G1 Phase; Humans; Lung Neoplasms; Phosphatidylinositol 3-Kinases; Signal Transduction; Sulfates

To evaluate the proliferation inhibitory effect of Lappaconitine (LAP) on non-small cell lung cancer cell line A549 cells in vitro and its possible mechanism.. A549 cell was cultured with different concentrations of LAP. Cellular proliferation was determined with MTT. Cell cycle and apoptosis were detected with FCM technology. The Cyclin E1 gene expression was checked by Real-time Quantitative PCR method.. LAP could inhibit the proliferation of A549 cells in vitro in a dose-dependent manner. LAP could induce apoptosis of A549 cell. Cell cycle was stopped at the G1 + G0 phase by LAP with FCM technology. With the increasement of LAP concentration, the ratio of G1 + G0 phase was increased and the ratio of S phase and G2 + M phase was decreased; The apoptotic rate was gradually increased, and the Cyclin E1 gene expression was down-regulated.. LAP has the inhibitory effect on the growth of A549 cells, which is related to the cell cycle arrest in G0/G1 phase, apoptosis and down-regulation of Cyclin E1 gene expression.

Topics: Aconitine; Aconitum; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin E; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal; Flow Cytometry; Humans; Lung Neoplasms; Real-Time Polymerase Chain Reaction; RNA, Messenger