Inhibitory effect of a novel naphthalimide-polyamine conjugate on proliferation of human hepatocellular carcinoma HepG2 cell line / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the effect of a novel naphthalimide-polyamine conjugate on apoptosis of human hepatocellular carcinoma HepG2 cell line. METHODS: MTT assay was used to evaluate the cell inhibition rate. The cellular morphous was detected with AO/EB/Hoechst staining, the ROS was detected with DCFH-DA staining, the mitochondrial membrane potential (ΔΨm) was detected with Rh123 staining, the expression of caspase-9 and PARP-1 was detected by immunofluorescence method. The cell cycle was detected by HCS. Apoptosis of HepG2 cells was quantified by flow cytometry using Annexin V/PI stain. RESULTS: Proliferation of HepG2 cells was inhibited significantly by the naphthalimide-polyamine conjugate in a dosage dependant manner. Under HCS, some HepG2 cells underwent a typical apoptotic morphologic change and the expression of ROS and caspase-9 was increased. The expression of PARP-1 and the mitochondrial membrane potential (ΔΨm) was detected decreased. Flow cytometry indicates 64.12% HepG2 cells were induced apoptosis after 48 h incubation with 25 μmol·L-1 naphthalimide-polyamine conjugate. CONCLUSION: The naphthalimide-polyamine conjugate could significantly induce the apoptosis of HepG2 cells by the mitochondrial pathway. The mechanism is concerned with increasing ROS, decreasing the mitochondrial membrane potential, upgrading caspase-9 and decreasing the expression of PARP-1.