L-securinine Induces Apoptosis In The Human Promyelocytic Leukemia Cell Line HL-60

Background: The Securinega alkaloids are a class of natural products isolated from plants of the Euphorbiaceae family. L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 cells indicating its potential as an efficient natural anti-tumor drug with low toxicity.Objective: To investigate the apoptotic effects of L-securinine in HL-60 cells and to explore its potential molecular mechanism as an anti-tumor agent.Methods: HL-60 cells were cultured with L-securinine. Proliferation and changes in morphology were evaluated by cell counting kit-8(CCK-8) assays and electron microscopy, respectively. Induction of apoptosis and cell cycle progression were investigated by flow cytometry(FCM). PI3K/AKT/m TOR pathway gene expression was measured by quantitative real-time(RT-PCR).Results: L-securinine decreased the viability of HL-60 cells in a dose- and time-dependent manner, with IC50 values at 24, 48 and 72 h post-treatment of 47.88, 23.85 and 18.87 μmol/L, respectively. Numerous apoptotic bodies were observed in HL-60 cells treated with 25 μmol/l L-securinine for 48 h. L-securinine at 12.5,25 and 50 μmol/L increased the rate of apoptosis in HL-60, cells and G1/S phase progression was retarded. Furthermore, L-securinine induced downregulation of PI3 K, AKT and m TOR gene expression and upregulation of PTEN gene expression in a dose-dependent manner.Conclusion: L-Securinine induces apoptosis and inhibition of cell cycle progression in HL-60 cells by modulation of PI3K/AKT/m TOR pathway gene expression. These observations indicate the potential of L-securinine as an anti-tumor agent.