Identification of a novel inhibitor of liver cancer cell invasion and proliferation through regulation of Akt and Twist1

Sci Rep. 2021 Aug 18;11(1):16765. doi: 10.1038/s41598-021-95933-4.

Abstract

When primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial-mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Proliferation / genetics
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • Antineoplastic Agents
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Proto-Oncogene Proteins c-akt