The Effect of Chaetoglobosins E on the Proliferation and Apoptosis of MCF-7 Cells and the Related Mechanisms

To explore the effect of Chaetoglobosins E (ChE) on tumor cell proliferation and apoptosis, human breast cancer MCF-7 cells, human bladder cancer T-24 cells, human melanoma C8161 cells and human leukemia U937 cells were treated with ChE of different concentrations for 24 h or 48 h. The MTT method was used to detect the proliferation of 4 kinds of tumor cells. To further study its mechanism of action, the Hoechst 33342 staining was used to observe the changes in the morphology of MCF-7 cells treated with ChE. Flow cytometry was used to detect the changes of apoptosis, cycle, reactive oxygen species and mitochondrial membrane potential of MCF-7 cells treated with ChE. The Western Blot method was used to detect the expression of apoptosis-related proteins in MCF-7 cells. The results showed that ChE inhibited the proliferation of MCF-7, T-24, C8161 and U937 cells in a time- and dose-dependent manner. Among the four tumor cells, ChE had the strongest inhibitory effect on the proliferation of MCF-7 with IC₅₀ of 82.04±7.01 μmol/L and 49.87±2.28 μmol/L at 24 h and 48 h, respectively. The Hoechst 33342 staining found that the number of apoptotic MCF-7 cells gradually increased, with significant characteristics of cell apoptosis and the volume of the nucleus was reduced, with the nucleus lysed and accompanied by apoptotic bodies with the increase of ChE concentration. The flow cytometry found that, after MCF-7 cells were treated with ChE, the number of apoptosis cells increased, the cell cycle was changed, the reactive oxygen species increased, and the mitochondrial membrane potential decreased. The Western Blot experiment found that the expression of Bid and Caspase 3 protein decreased and cleaved Caspase 3 and the ratio of Bax protein to Bcl-2 protein expression increased. To sum up, ChE-induced apoptosis of MCF-7 cells is related to the Caspase-dependent mitochondrial pathway.