title: L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway.
abstract: 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 indicating its potential as an efficient natural antitumor drug with low toxicity. The aim of the present study was to investigate the apoptotic effects of L-securinine on HL-60 cells and to explore its potential underlying molecular mechanism(s) as an antitumor agent. HL-60 cells were cultured with L-securinine. The proliferation and changes in cell morphology were evaluated by cell counting Kit-8 (CCK-8) assay and electron microscopy, respectively. Induction of apoptosis and cell cycle progression were investigated by flow cytometry. The PI3K/AKT/mTOR pathway gene expression was measured by quantitative PCR (qPCR). 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 the 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 PI3K, AKT and mTOR gene expression and upregulation of PTEN gene expression in a dose-dependent manner. In conclusion, L-securinine induces apoptosis and inhibition of cell cycle progression in HL-60 cells by modulation of the PI3K/AKT/mTOR pathway gene expression. These observations indicate the potential of L-securinine as an antitumor agent.
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui, P.R. China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui, P.R. China.
authors.forename: Maidong
authors.initials: M
authors.lastname: Li
authors.affiliation: The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, P.R. China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, P.R. China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.affiliation: The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, P.R. China.
authors.forename: Zhaoning
authors.initials: Z
authors.lastname: Ji
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D018922:HL-60 Cells; D006572:Heterocyclic Compounds, Bridged-Ring / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D010880:Piperidines / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001381:Azepines; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010880:Piperidines; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C494929:PTEN protein, human; C000785:securinine