Objectives: Tetrazanbigen (TNBG) is a newly synthesized compound with an isoquinoline moiety, and its antitumour effects were evaluated in in-vitro and in-vivo models.
Methods: 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure the antiproliferative activity of TNBG on cancer cell lines. Antitumour activity of TNGB in vivo was also assessed in a xenograft model of human hepatocellular carcinoma QGY-7701 cell line. Cell cycle and cell apoptosis analysis was performed.
Key findings: TNBG exhibited strong antitumour efficacy against six human cancer cell lines with IC50 range of 2.13-8.01 μg/ml. The IC50 of TNBG on normal hepatic cells was 11.25 μg/ml. Lots of lipid droplets were observed in cytoplasm of human hepatocellular carcinoma QGY-7701 cells after treatment of TNBG. S phase arrest and apoptosis induction by TNBG were also found on QGY-7701 cells. Intraperitoneal injection of TNBG (1.5 mg/kg/day) resulted in significant decreases in tumour volume and tumour weight on nude mice bearing QGY-7701 cells xenografts. Results from pathological analysis in nude mice demonstrated that TNBG could induce lipid accumulation specifically in cancer tissue rather than in other normal organs, tissues and blood.
Conclusions: These results suggested that TNBG might exert potent antitumour activity through inducing lipid accumulation in cancer cell.
Keywords: antitumour effect; human hepatocellular carcinoma; lipid accumulation; tetrazanbigen.
© 2015 Royal Pharmaceutical Society.