p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells

Mol Med Rep. 2016 Oct;14(4):3855-61. doi: 10.3892/mmr.2016.5696. Epub 2016 Aug 31.

Abstract

The present study aimed to investigate the effects of berberine hydrochloride on the proliferation and apoptosis of HeLa229 human cervical cancer cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine the cytotoxicity of berberine hydrochloride against HeLa229 cells. The effects of berberine hydrochloride on the apoptosis of HeLa229 cells was detected by immunofluorescence and flow cytometry, and the mRNA expression levels of p53, B‑cell lymphoma 2 (Bcl‑2) and cyclooxygenase‑2 (cox‑2) were analyzed by reverse transcription-quantitative polymerase chain reaction. Berberine hydrochloride inhibited the proliferation of HeLa229 cells in a dose‑dependent manner; minimum cell viability (3.61%) was detected following treatment with 215.164 µmol/l berberine hydrochloride and the half maximal inhibitory concentration value was 42.93 µmol/l following treatment for 72 h. In addition, berberine hydrochloride induced apoptosis in HeLa229 cells in a dose‑ and time‑dependent manner. Berberine hydrochloride upregulated the mRNA expression levels of p53, and downregulated mRNA expression levels of Bcl‑2 and cox‑2, in a dose‑dependent manner. In conclusion, berberine hydrochloride inhibited the proliferation and induced apoptosis of HeLa229 cells, potentially via the upregulation of p53 and the downregulation of Bcl‑2 and cox‑2 mRNA expression levels.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Berberine / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cervix Uteri / drug effects
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Cyclooxygenase 2 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Berberine
  • Cyclooxygenase 2