Effects of lycorine on HL-60 cells via arresting cell cycle and inducing apoptosis.
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.
Liu
Jing
J
Molecular Biology Research Center, Xiangya Medical College, Central South University, Changsha, Hunan 410078, PR China.
Hu
Wei-Xin
WX
He
Li-Fang
LF
Ye
Mao
M
Li
Yan
Y
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
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