[Anti-leukemia effect of oridonin on T-cell acute lymphoblastic leukemia].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2014 Nov ;45(6):903-7. PMID: 25571712
OBJECTIVE: To investigate the antileukemia effect of oridonin on T-cell acute lymphoblastic leukemia cell line CEM.
METHODS: Human T-cell acute lymphoblastic leukemia cell line CEM was cultured in vitro. The 50% inhibition concentration (IC50) of oridonin against CEM cells was examined using modified MTT assay. The cellular morphologic changes were observed using a light microscope. The percent of apoptosis of CEM cells after drug treatment was evaluated by flow cytometric analysis. The active levels of AKT/mTOR, RAF/MEK/ ERK, STAT5 signaling pathways and the expression levels of Bcl-2 and BAX were examined by Western blot.
RESULTS: Oridonin inhibited the growth of CEM cells in time- and dose dependent manner and the ICs0 of oridonin was (7. 37± 1. 99) μmol/L after 72 h treatment. The cellular membrane of CEM cells treated with oridonin became unsharp, some of them disintegrated. Oridonin induced apoptosis in CEM cells and the percent of apoptosis rate after 0, 5, 7.5, 10 μmol/L oridonin treatment for 24 h were (4. 8±2. 11)%, (19.03±12.54)% ,(40.27± 3.31) / and (57. 23 ± 6. 69)% respectively. Oridonin inhibited activation of mTOR, P70S6, 4EBP1, RAF. ERK and STAT5 signaling protein, which were constitutively activated in CEM cells, however, oridonin had no inhibitory effect on AKT kinase. Oridonin down-regulated the level of anti apoptotic protein Bcl-2 and up-regulated the expression of pro-apoptotic protein Bax.
CONCLUSION: Oridonin exerted antileukemia effect in CEM cells by inhibiting the activation of mTOR/P70/4EBP1, RAF/ERK and STATS signaling pathways, down-regulating the expression of Bel-2 and up-regulating the expression of BAX.