Effect of Piper cubeba total extract and isolated lignans on head and neck cancer cell lines and normal fibroblasts

J Pharmacol Sci. 2022 Jan;148(1):93-102. doi: 10.1016/j.jphs.2021.09.002. Epub 2021 Oct 7.

Abstract

The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 μg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.

Keywords: Anti-inflammatory agents; Bioactive compounds; Phytotherapy.

MeSH terms

  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects*
  • Fibroblasts / physiology*
  • Gene Expression / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Lignans / chemistry
  • Lignans / isolation & purification*
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Molecular Targeted Therapy
  • Phytotherapy*
  • Piper / chemistry*
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Time Factors

Substances

  • Lignans
  • Piper cubeba extract
  • Plant Extracts