Inhibitory effect and mechanism of MDCI,a novel β-elemene derivative,on the proliferation of hepatocellular carcinoma cells
Objective β-elemene is an innovative drug with independent intellectual property rights in China,but its effective concentration is high and its anticancer efficiency is low.The aim of this study was to screen β-elemene derivatives with high anti-hepatocellular carcinoma activity and reveal the cytological mechanism of their inhibition of malignant phenotype of hepatocellular carcinoma cells.Methods Human liver cancer cell MHCC97-H was selected as the experimental object,and the cells were treated with β-elemene,MDCC,MCMC,and MDCI.The cells activities were evaluated by CCK-8 assay.After comparison,we found MDCI had the strongest inhibition on liver cancer cells,and selected MDCI for further study.The morphological changes of the cells were tracked and monitored under the microscope,and the effects on cell migration were detected by cell scratch test.EdU fluorescence staining was used to determine the effects on DNA replication of liver cancer cells.The effects on cell cycle were measured by flow cytometry,and the effects of the cell death-inducing effect of MDCI were evaluated by live/dead cell fluorescence staining.Apoptosis was detected by Annexin-V-FITC apoptosis kit.Results The inhibitory capacity of three β-elemene derivatives on hepatocellular carcinoma cells was improved in different degrees compared with β-elemene,and MDCI had the strongest inhibitory capacity on hepatocel-lular carcinoma cells.Increasing the concentration and incubation time of MDCI resulted in a significant inhibition of MHCC97-H cell activity,while migration ability remained relatively unchanged(F=2.636,P>0.05).It has been demon-strated that MDCI reduces the rate of DNA replication(F=133.100,P<0.001),thereby blocking cell cycle progression into the S phase(F=224.500,P<0.001).At a concentration of 10μM,MHCC97-H cells began to undergo apoptosis as the primary mode of cell death.Conclusions We have screened a novel β-elemene derivative,MDCI,which exhibits excellent inhibitory effects on hepatocellular carcinoma cells.At low concentrations,MDCI primarily inhibits DNA synthesis to block cell cycle progression and thus suppress excessive cell proliferation.At high concentrations,it primarily induces cell apoptosis to kill tumor cells.This research results suggest that MDCI has good potential to be a novel lead compound for liver cancer treatment,which has positive implications for enriching the drug pipeline for liver cancer treatment.
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