ABSTRACT
Objective To analyze inhibitory effect of taspine derivative TasD1-6 on human liver cancer cells of Hep3B, HepG2, and BEL7402, and to study their preliminary mechanism of anticancer action. Methods Effect of TasD1-6 on cell growth of Hep3B, HepG2, and BEL7402 were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and real-time cellular analysis (RTCA) assay. Effect of TasD1-6 on Hep3B cell morphology was investigated with crystal violet staining. Next, Hep3B cell apoptosis was analyzed by Annexin V FITC/PI and Hoechst 33258 staining. Flow cytometry was used to determine Hep3B cell cycle. Effect of TasD1-6 on cell apoptosis protein expression in Hep3B cell was determined by Western blotting. Results MTT and RTCA assay demonstrated that TasD1-6 significantly inhibited the growth of Hep3B cell and the IC50 was (11.3 ± 1.6) μmol/L. Hep3B cell morphology indicated the shrinkage and obvious morphology changes. And TasD1-6 induced the Hep3B cell apoptosis in dose-dependent manner. Cell was stopped as G1 phase by TasD1-6. Western blotting analysis showed TasD1-6 could upregulate the protein expression of p53 and Bax and downregulate Mcl-1 protein expression (P < 0.05). Conclusion Taspine derivative TasD1-6 shows better inhibitory action on the growth of human liver cancer Hep3B cell than HepG2 and BEL7402 cells. At the same time, TasD1-6 can change cell cycle and induce cell apoptosis, which probably related to upregulation of p53 and Bax protein expression and downregulation of Mcl-1 protein expression.