Inhibition And Mechanism Of Glycyrrhetinic Acid Derivatives On MCF-7

GZ-107 is a new compound with a variety of bioactivity which derives from 18?-Glycyrrhetinic acid.This paper studied or discussed its anti-cancer activity in vivo and possible mechanisms.MTT assay was used to discuss the effect of GZ-107 on human breast cancer MCF-7 cells.The result indicated that when MCF-7 cells were exposed to various concentrations of GZ-107 for different incubation time,the cellular cytotoxicities were significantly increased in a time-and dose-dependent manner.What was more,it was significantly visible that cells with GZ-107 treatment became shrunken and nonadhesive while cells in control group remained normal shape.PI staining was applied to preliminary research whether MCF-7 was induced apoptosis by GZ-107.It showed that GZ-107 might induce apoptosis in MCF-7 cells while the cells exposed to GZ-107 emanating red fluorescent light were more than the control group.Flow cytometry analysis was applied to further discuss apoptotic cells after the treatment of MCF-7.The percentage of apoptotic cells was.increased from 13.07%to 22.18%and 46.10%after 48 h of treatment with 10,25 and 50?M GZ-107,compared with the control of 4.13%.These results showed that the apoptosis ratio was increased with concentrations of GZ-107.Western blot analysis was used to investigate the expression of cell apoptosis related proteins.With the increasing of GZ-107 concentrations,the procaspase-3 and Bcl-2 were decreased significantly,while the Bax increased.Results showed the diminution of the Bcl-2/Bax ratio.Furthermore,GZ-107 treatment increased phosphorylated p38 and phosphorylated ERK1/2 levels in MCF-7 cells in a concentration-dependent manner,which indicated that the apoptosis might relate to the expression of MAPK proteins.Flow cytometry analysis was also applied to discuss the effct caused by GZ-107 treatment on cell cycle.The result showed that the inhibitory effect against the proliferation of MCF-7 cells was partly due to the cell cycle arrest.In GZ-107-treated cells,the number of cells in G1 phase(25?M,66.33%;50?M,80.98%)was significantly increased.In contrast,60.19%of cells were in G1 phase in the control group.Furthermore,GZ-107 led to a corresponding decrease in the cells in S phase.(control,28.14%;25?M,17.69%;50?M,14.91%)Western blot analysis was performed to investigate the expression of cell cycle regulator proteins.The result showed that the p21 protein level was increased after 48 h incubation with GZ-107 in a dose-dependent manner.Simultaneously,a dose-dependent down-regulation of cyclinA and cyclin B1 and up-regulation of pCdc2 was observed.The expression of Cdc2 had no change.It indicates that the GZ-107 induced mcf-7 cells cycle distribution through the regulation of the expression and activity of these proteins.In conclusion,our findings indicate the inhibitory effect of GZ-107 on the proliferation of the human Breast cancer(MCF-7)cells.The inhibitory mechanisms may include induction of apoptosis and cell cycle arrest.The derivative of 18?-Glycyrrhetinic acid is a potential compound which may fight against breast cancer.