TNBG-5602, a novel derivative of quinoxaline, inhibits liver cancer growth via upregulating peroxisome proliferator-activated receptor γ in vitro and in vivo

J Pharm Pharmacol. 2019 Nov;71(11):1684-1694. doi: 10.1111/jphp.13159. Epub 2019 Aug 25.

Abstract

Objectives: TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism.

Methods: The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701.

Key findings: The results of CCK-8 assay showed that TNBG-5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG-5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG-5602 could remarkably inhibit the growth of tumours. During in-vitro and in-vivo studies, we noted that TNBG-5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG-5602 may be exerted through activating peroxisome proliferator-activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA).

Conclusions: Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.

Keywords: TNBG-5602; anticancer; lipid accumulation; peroxisome proliferator-activated receptor γ; proliferating cell nuclear antigen.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Azo Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Female
  • Gonanes / pharmacology*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Nude
  • PPAR gamma / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Quinoxalines / pharmacology*
  • Up-Regulation / drug effects*

Substances

  • Antineoplastic Agents
  • Azo Compounds
  • Gonanes
  • PPAR gamma
  • Proliferating Cell Nuclear Antigen
  • Quinoxalines
  • tetrazanbigen