In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-κB activation in HL-60 cells  

作　　者：Min LI Wan SUN Ya-ping YANG Bo XU Wen-yuan YI Yan-xia MA Zhong-jun LI Jing-rong CUI 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Beijing 100191, China [2]Department of Chemical Biologyj School of Pharma-ceutical Sciences (Peking University), Beijing 100191, China

出　　处：《Acta Pharmacologica Sinica》2009年第1期134-140,共7页中国药理学报（英文版）

摘　　要：Aim： To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative （STA-35） on HL-60 cells in vitro. Methods： TNF-α-induced NF-κB activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-κB p65 and its inhibitor IκB were viewed by Western blotting. Results： STA-35 （1-20 μmol/L） suppressed TNF-α-induced NF-κB activation in transfected cells （HEK293/pNiFty-SEAP） in a dose- （1-20 μmol/L） and time-dependent （0-48 h） manner. It was also shown that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell proliferation with an IC50 value of 9.05 lamol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase （PARP） cleavage. Subsequently, both NF-κB p65 and its inhibitor IκB gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-κB translocation induced by TNF-α from the cytoplasm to the nucleus. Conclusion： A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-κB activation.Aim： To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative （STA-35） on HL-60 cells in vitro. Methods： TNF-α-induced NF-κB activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-κB p65 and its inhibitor IκB were viewed by Western blotting. Results： STA-35 （1-20 μmol/L） suppressed TNF-α-induced NF-κB activation in transfected cells （HEK293/pNiFty-SEAP） in a dose- （1-20 μmol/L） and time-dependent （0-48 h） manner. It was also shown that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell proliferation with an IC50 value of 9.05 lamol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase （PARP） cleavage. Subsequently, both NF-κB p65 and its inhibitor IκB gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-κB translocation induced by TNF-α from the cytoplasm to the nucleus. Conclusion： A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-κB activation.

关 键 词：ANTICANCER HL-60 THALIDOMIDE NF-ΚB apoptosis 

分 类 号：R971.3[医药卫生—药品]