A novel stilbene derivative (GMQ3) suppressed proliferation and induced apoptosis in lung cancer via the p38-MAPK/SIRT1 pathway

Biochem Pharmacol. 2021 Nov:193:114808. doi: 10.1016/j.bcp.2021.114808. Epub 2021 Oct 19.

Abstract

Lung cancer is the primary cause of cancer-related mortality worldwide. The anticancer effect of stilbene has been noted in various tumor types. GMQ3, which has a stilbene-mimicking skeleton, is a novel small-molecule compound with promising antitumor activity. Our results revealed that GMQ3 not only suppressed cell proliferation and cell migration of lung cancer cells but also led to G1 phase cell cycle arrest and triggered caspase-dependent apoptosis. Furthermore, investigation of the molecular mechanism showed that GMQ3 could inhibited proliferation and induced apoptosis via the p38-MAPK/SIRT1 pathway both in vitro and in vivo. Xenograft tumor mouse models showed that GMQ3 significantly inhibited tumor growth in vivo without affecting body weight. Our findings indicated that GMQ3 exerts a strong anticancer action by suppressing cell proliferation, inhibiting cell migration and inducing cell apoptosis. Moreover, the efficacy of GMQ3 was enhanced in the presence of CDK4/6 inhibitor Abemaciclib. We conclude that GMQ3 is a promising agent with potential for lung cancer.

Keywords: Cell apoptosis; Cell cycle; Lung cancer; Stilbene; p38-MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mice, Nude
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Aminopyridines
  • Antineoplastic Agents
  • Benzimidazoles
  • Stilbenes
  • abemaciclib
  • Sirt1 protein, mouse
  • Sirtuin 1