2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Cell Physiol Biochem. 2018;50(3):883-892. doi: 10.1159/000494474. Epub 2018 Oct 24.

Abstract

Background/aims: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC).

Methods: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo.

Results: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo.

Conclusion: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application.

Keywords: Apoptosis; IL-6/STAT3; MM1; Magnolol; OSCC.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use
  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Interleukin-6 / metabolism
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Transplantation, Heterologous
  • Vimentin / metabolism

Substances

  • Biphenyl Compounds
  • Cadherins
  • Interleukin-6
  • Lignans
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Vimentin
  • magnolol
  • Caspase 3