Novel agent #2714 potently inhibits lung cancer growth by suppressing cell proliferation and by inducing apoptosis in vitro and in vivo

Mol Med Rep. 2019 Jun;19(6):4788-4796. doi: 10.3892/mmr.2019.10114. Epub 2019 Apr 2.

Abstract

The use of small molecule compounds to inhibit cell proliferation is one of the most promising approaches in cancer therapy. In the present study, a cell viability assay, flow cytometry analysis, western blotting and mouse xenograft models were used to investigate the anticancer activities of #2714 and its underlying mechanisms in lung cancer. The present in vitro results suggested that #2714 significantly inhibited the viability of the human non‑small cell lung cancer line SPC‑A1 in a concentration‑ and time‑dependent manner, with a half‑maximal inhibitory concentration value of 5.54 µM after 48 h of treatment. Additionally, #2714 inhibited SPC‑A1 cell proliferation via the Wnt/β‑catenin pathway and by impairing mitochondrial membrane potential. The protein expression levels of Wnt 3a, Wnt 5a/b, phosphorylated (p)‑β‑catenin, p‑glycogen synthase kinase 3β, and p‑mitogen‑activated protein kinase 14 were downregulated following treatment with #2714. Furthermore, using a mouse xenograft model, #2714 was identified to significantly inhibit tumor growth and to decrease cancer cell proliferation in vivo. #2714 may represent a novel effective anticancer compound targeting lung cancer cells. Additionally, #2714 was able to induce apoptosis and decrease cell proliferation in SPC‑A1 cells via the Wnt/β‑catenin pathway.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Phosphorylation
  • Wnt Signaling Pathway / drug effects
  • Wnt-5a Protein / metabolism
  • Wnt3A Protein / metabolism
  • beta Catenin

Substances

  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Wnt-5a Protein
  • Wnt3A Protein
  • beta Catenin