The mechanism for SYUNZ-4 inducing apoptosis of U937 cells

Objective To investigate apoptotic effect of SYUNZ-4 on U937 cells , and its molecular mechanism. Methods Cell proliferation and viability were detected by MTT trypan blue exclusion assay. DNA electrophoresis, fluorescence microscopy and FACS were used to detect apoptosis. Apoptosis related proteins were analyzed by Western blot. Results The inhibition of cell proliferation in U937 cells exposed to SYUNZ-4 was dose- and time- dependent. SYUNZ-4 induced DNA ladder, nuclear condensation and apoptotic bodies and significantly increased apoptosis in U937 cells when exposed a dose of 6μg/ml for 6, 12 and 24 h, the apoptotic cells were(12.2±6. 5)% ,(25. 3±11.4)% ,and (25. 3±11. 4)% ,respectively, which was markedly higher than that of control [ (2. 1±0. 8) % ] ( P 0. 05 ). SYUNZ-4 activated caspase-3, caspase-8, caspase-9 and PARP, up-regulated proteins level of Fas, FasL, Bax, P21 and P27, down-regulated expression of Bcl-xL, while had no effect on gene of Bcl-2 and BID. Conclusion Shikonin derivative-SYUNZ-4 can induce U937 leukemic cell apoptosis in vitro through activation of caspase family and related signal molecules.