Effects of honokiol on the proliferation and apoptosis of human acute leukemia U937 cells

Objective To detect the mechanism of the growth inhibition and apoptosis of human acute leukemia cell line U937 cells induced by honokiol.Metheds The proliferation inhibition was detected by MTT method.Cell apoptosis was tested by Hoechst 33342 staining and flow cytometry with Annexin V/PI staining.RT-PCR was used to detect the mRNA expression of the apoptosis gene Bcl-2,Bax,Caspase 3,Caspase 8 and Caspase 9.Results The inhibition effect of honokiol(5 μg/ml,48 h) on U937 cells proliferation could he observed,and the inhibition rate of 10 μg/ml honokiol on cell proliferation reached above 50％ (48 h).U937 cells proliferation could be completely inhibited for 120 h. U937 cells apoptosis rate reached 26.8％ (P ＜0.01)after being treated with 10 μg/ml honokiol.After being treated with 10 μg/ml honokiol for 48 h,the Bcl-2 gene expression in U937 cells was reduced (control group:0.33 ± 0.02,experimental group:0.14 ±0.01,P ＜ 0.01 ),and the Bax gene expression was elevated ( control group:0.1 ± 0.01,experimental group:0.87 ± 0.08,P ＜ 0.01 ).The gene expressions of Caspase 3 ( control group:0.48 ± 0.01,experimental group:0.87±0.06,P ＜0.01),Caspase 8(control group:0.23±0.02,experimental group:0.41 ±0.07,P ＜ 0.01 ) and Caspase 9 ( control group:0.44 ± 0.05,experimental group:0.76 ± 0.06,P ＜ 0.01 ) were all increased.The activity of Caspase-3 was 0.325 ±0.089,which was significantly higher than that of the control group ( P ＜0.01 ).Conclusion Honokiol can significantly inhibit the proliferation and induce cell apoptosis of human acute leukemia cell line U937 cells.The mechanism is related to the up-regulation of Bax and down-regulation of Bcl-2,and the endogenous and exogenous pathways are both inolved in the apoptosis process. Key words: Honokiol; Leukemia; U937 cells; Cell proliferation; Cell apoptosis