EF-24 inhibits TPA-induced cellular migration and MMP-9 expression through the p38 signaling pathway in cervical cancer cells

Environ Toxicol. 2023 Feb;38(2):451-459. doi: 10.1002/tox.23709. Epub 2022 Nov 22.

Abstract

Diphenyl difluoroketone (EF-24), a synthetic curcumin analog, has enhanced bioavailability over curcumin. EF-24 acts more powerful bioactivity for anti-inflammatory and anti-cancer activity. However, the effects and mechanism of EF-24 on cervical cancer has not been fully investigated. Herein, this study evaluated the effects of EF-24 on TPA-induced cellular migration of cervical cancer. The results showed that EF-24 substantially reduced the cellular migration and cellular invasion of the HeLa and SiHa cells. Moreover, gelatin zymography, western blotting analyses and real-time PCR revealed that EF-24 suppressed Matrix metalloproteinase-9 (MMP-9) activity, protein expression and mRNA levels. Mechanistically, EF-24 inhibited the phosphorylation of the p38 signaling pathway. In conclusion, EF-24 inhibited TPA-induced cellular migration and cellular invasion of cervical cancer cell lines through modulating MMP-9 expression via downregulating signaling p38 pathway and EF-24 may have potential to serve as a chemopreventive agent of cervical cancer.

Keywords: EF-24; MMP-9; cervical cancer; invasion; migration.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Curcumin* / analogs & derivatives
  • Curcumin* / pharmacology
  • Female
  • Humans
  • Matrix Metalloproteinase 9* / genetics
  • Matrix Metalloproteinase 9* / metabolism
  • Neoplasm Invasiveness
  • Signal Transduction
  • Uterine Cervical Neoplasms* / enzymology
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Curcumin
  • Matrix Metalloproteinase 9