Deguelin blocks cells survival signal pathways and induces apoptosis of HL-60 cells in vitro.
To investigate the anti-cancer effects and molecular mechanism of deguelin on the human leukemia HL-60 cells, to explore the expression and clinical significance of p-AKT, survivin and Bcl-2 in leukemia cell line HL-60 cell. Cell growth rate was assessed by MTT assay. Apoptotic index was evaluated by TUNEL staining. Apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit and transmission electron microscopy (TEM), expression of p-Akt, Bcl-2 and surviving in HL-60 cells was checked by Western blot. Deguelin presented striking proliferation inhibition potency on HL-60 cells in vitro, with the I(C50) value for 48 h being 20.14 nM, and induced apoptosis in HL-60 in a concentration-time-dependent manner. Apoptotic bodies and cell shrinkage and fragmentation were observed by TUNEL and TEM. Deguelin-induced cells morphological changes and degraded several kinase proteins, including Bcl-2 and survivin (members of lap). The degradation of these kinases blocked PI3K/Akt survival signal pathways, inducing apoptosis. Deguelin may induce HL-60 cell apoptosis through depletion of multiple kinase proteins and blockage of survival signal pathways of HL-60 cells.
Chen
Yan
Y
Institute of Hematology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. yanchen@public.wh.hb.cn
Wu
Qing
Q
Cui
Guo-hui
GH
Chen
Yi-quan
YQ
Li
Rui
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D011494:Protein Kinases; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D012402:Rotenone; D011494:Protein Kinases; C107676:deguelin