Garcinol inhibits tumour cell proliferation, angiogenesis, cell cycle progression and induces apoptosis via NF-κB inhibition in oral cancer

Tumour Biol. 2016 Jun;37(6):7175-84. doi: 10.1007/s13277-015-4583-8. Epub 2015 Dec 12.

Abstract

Garcinol, a polyisoprenylated benzophenone is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Its ability to inhibit tumour growth has been demonstrated in certain cancers. In this study, we evaluated the potential anti-tumour effects of garcinol on oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines (SCC-4, SCC-9 and SCC-25) were treated with garcinol for 48 h and its effect on growth and proliferation, clonogenic survival, cell cycle and apoptosis was studied by MTT, clonogenic assay, propidium iodide (PI) staining and annexin-V binding assay, respectively. The alteration in expression of NF-κB and COX-2 was studied by western blot analysis and that of VEGF by ELISA. Garcinol treatment significantly (p < 0.001) inhibited the growth and proliferation and colony formation of OSCC cells with a concomitant induction of apoptosis and cell cycle arrest. It did not show toxic effect on normal cells. It significantly (p < 0.05) reduced the expression of NK-κB and COX-2 expression in treated cells as compared to untreated controls besides inhibiting VEGF expression. It appears that garcinol exerts anti-proliferative, pro-apoptotic, cell-cycle regulatory and anti-angiogenic effects on oral cancer cells through inhibition of NF-κB and COX-2. Thus, garcinol may be developed as a potential chemopreventive and/or chemotherapeutic agent for treatment of oral squamous cell carcinoma.

Keywords: Apoptosis; COX-2; Cell cycle; Garcinol; NF-κB; Oral cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Biomarkers, Tumor
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Plant Extracts / pharmacology
  • Terpenes / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • NF-kappa B
  • Plant Extracts
  • Terpenes
  • garcinol