Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells

In Vivo. 2005 Jan-Feb;19(1):247-52.

Abstract

Background: We have previously shown that berberine exerts its anti-inflammatory effects through inhibition of cyclooxygenase-2 (COX-2) expression. In this study, we explored the biochemical influence of berberine-induced COX-2 reduction and apoptosis.

Materials and methods: KB cells were treated with berberine, and the apoptosis was measured by morphology and caspase-3 activity. The effects of prostaglandin E2 (PGE2) on berberine-mediated cell growth were also determined. The expression of COX-2, Bcl-2, Mcl-1, Akt and phosphorylated Akt in berberine-treated KB cells, with or without PGE2, were assessed by Western blots.

Results: Berberine induced apoptosis in KB cells, and was partially reversed by incorporation of PGE2. Berberine treatment inhibited COX-2 and Mcl-1 expression dose-dependently, but not Bcl-2. PGE2 induced COX-2 and Mcl-1 expression and reversed the repressive effect of berberine on Mcl-1. In addition, PGE2 had no effect on total Akt, but slightly reversed the phosphorylated Akt, which was decreased by berberine.

Conclusion: These results suggest that berberine-induced apoptosis might be COX-2-dependent and is related to decreased Akt phosphorylation and Mcl-1 expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Berberine / pharmacology*
  • Carcinoma / drug therapy
  • Carcinoma / pathology
  • Caspase 3
  • Caspases / drug effects
  • Caspases / metabolism
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • KB Cells
  • Membrane Proteins
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / metabolism*
  • Phosphorylation / drug effects
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Serine-Threonine Kinases / drug effects
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Membrane Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Berberine
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Dinoprostone