title: Effects of lycorine on HL-60 cells via arresting cell cycle and inducing apoptosis.
abstract: As a natural anti-cancer alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. The survival rate of HL-60 cells exposed to lycorine was decreased in a dose-dependent manner with 1 microM as the 50% inhibitory concentration (IC50), cell growth was slowed down by arresting cell cycle at G2/M phase, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic morphological changes, apoptotic DNA "ladder" pattern, and sub-G1 peak in cell phase distribution, showing apoptosis of HL-60 cells. To further understand the apoptotic molecular mechanism of lycorine on HL-60 cells, caspase activity was tested by colorimetric assay, and the expression of Bcl-2 and Bax proteins was examined by Western blotting. The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis. Our finding suggests that lycorine can suppress leukemia growth and reduce cell survival via arresting cell cycle and inducing apoptosis of tumor cells.
authors.affiliation: Molecular Biology Research Center, Xiangya Medical College, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Hu
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: He
authors.forename: Mao
authors.initials: M
authors.lastname: Ye
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival; D003124:Colorimetry; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D008856:Microscopy, Fluorescence; D010617:Phenanthridines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D010617:Phenanthridines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020169:Caspases; C015330:lycorine