Honokiol Is a Potential Therapeutic Agent and Has a Synergistic Effect With 5-FU in Human Urothelial Cell Carcinoma Cells

Anticancer Res. 2019 Dec;39(12):6555-6565. doi: 10.21873/anticanres.13871.

Abstract

Background/aim: Honokiol is a biphenolic component of the bark of Magnolia, and has been shown to exert several activities, including anti-depressant, anti-emetic, anti-oxidative, anti-thrombotic, anti-angiogenesis, anti-anxiolytic, anti-inflammatory and anti-tumor effects.

Materials and methods: The anti-tumor activities of honokiol and its synergistic effect with 5-fluorouracil (5-FU) in human urothelial cell carcinoma (UCC) cells were investigated.

Results: Honokiol significantly suppressed the proliferation of UCC cells in a dose- and time-dependent manner. Moreover, honokiol inhibited the tumorigenesis of UCC cells in vitro. In addition, honokiol induced cell cycle arrest at G0/G1 phase and caused apoptosis of UCC cells through the intrinsic pathway. Importantly, we demonstrated that honokiol potentiated the cytotoxic effect of 5-FU, and displayed a synergistic effect with 5-FU in UCC cells.

Conclusion: Honokiol causes growth inhibition, tumorigenesis suppression, cell cycle arrest, apoptosis, and importantly has a synergistic effect with 5-FU in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC.

Keywords: Honokiol; apoptosis; cell cycle arrest; synergistic effect; urothelial cell carcinoma.

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Biphenyl Compounds / pharmacology*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lignans / pharmacology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Biphenyl Compounds
  • Lignans
  • honokiol
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Fluorouracil