Oxymatrine (Omt) Inhibits Lung Cancer Growth Through Mitogen Activated Protein Kinase Jnk/Erk/P38mapks Activation

The present study investigated oxymatrine for anti-proliferative ability against lung cancer cells in vitro and explored related mechanism. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis using annexin V-FITC staining. The ROS production was monitored using carboxy-H2-DCFDA and protein expression by western blotting. Oxymatrine at 16 mu M reduced H1975 and A549 cell proliferation to 32.76 and 29.38%, respectively. In oxymatrine treated cells caspase-3 activity and apoptosis was significantly (p < 0.05) increased compared to control. In oxymatrine treated H1975 and A549 cells a marked promotion in p-p38 and p-JNK1/2 protein level and suppression of p-ERK 1/2 level was observed. Exposure of H1975 and A549 cells to PD169316 (p38 inhibitor) and SP600125 (JNK inhibitor) at 5 mM doses significantly alleviated oxymatrine (16 FM) mediated elevation of caspase-3 activity. Production of ROS was much higher in oxymatrine treated H1975 and A549 cells compared to control cells. The oxymatrine mediated ROS production up-regulation was inhibited in H1975 and A549 cells on pre-treatment with NAC. In FeTMPyP-pretreated cells increase in p-p38 and p-JNK expression by oxymatrine (16 mu M) was completely alleviated. Thus oxymatrine inhibits lung cancer proliferation in vivo by oxidative response induced cell apoptosis. The p38/JNK activation was promoted and ERK 1/2 phosphorylation inhibited by oxymatrine in H1975 and A549 cancer cells. Therefore, oxymatrine has anti-proliferative activity against lung cancer cells which needs to be studied using in vivo studies.