| Alpha-calendic acid and ?-calendic acid,geometric and positional isomers of linolenic acid were previously shown to possess potent anticancer properties.In this study,we investigated the effects of ?-calendic acid and ?-calendic acid on apoptosis and migration of human choriocarcinoma JEG-3 cells in vitro,and explored its mechanisms.The MTT and LDH assay results showed that incubation with ?-calendic acid and?-calendic acid caused a dose-and time-dependent decrease of JEG-3 cells viability,and caused cell toxicity.Hoechst 33342 staining and flow cytometry analysis showed that?-calendic acid and ?-calendic acid induced apoptosis of human choriocarcinoma JEG-3 cells.The apoptosis rates are 54.10%±1.05%and 50.03%± 1.00%when treated with 40?mol/L?-calendic acid and ?-calendic acid.Transwell assay and wound healing showed that?-calendic acid and ?-calendic acid inhibited migration of JEG-3 cells,the inhibitory rates are 28.13%±2.82%and 20.68%±2.82%by 40?gmol/L a-calendic acid and ?-calendic acid treatment.Treatment with a-calendic acid and ?-calendic acid significantly increased oxidative stress in human choriocarcinoma JEG-3 cells by detecting the level of reactive oxygen species(ROS),lipid peroxidation production malondialdehyde(MDA),glutathione(GSH)and the effects of antioxidants NAC and a-tocopherol.Furthermore,oxidative stress activated the phosphorylation of p38 MAPK.SB203580,a selective p38 MAPK inhibitor,blocked the apoptosis induced by a-calendic acid and ?-calendic acid through up-regulating Bcl-2/Bax ratio and inhibited the activation of Caspase-3 and Caspase-9.Besides,SB20350 also partially abrogated the cell invasion effects of a-calendic acid and ?-calendic acid.These results suggested that a-calendic acid and P-calendic acid induced apoptosis and inhibited invasion in JEG-3 cells by oxidative stress and subsequent activation of P38 MAPK. |
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