Berberine enhances the anti‑tumor activity of tamoxifen in drug‑sensitive MCF‑7 and drug‑resistant MCF‑7/TAM cells

Mol Med Rep. 2016 Sep;14(3):2250-6. doi: 10.3892/mmr.2016.5490. Epub 2016 Jul 8.


Berberine, an isoquinoline alkaloid, has been previously demonstrated to possess anti‑breast cancer properties. Tamoxifen is widely used in the prevention and treatment of estrogen receptor-positive breast cancer. Thus, the aim of the present study was to assess whether berberine enhanced the anticancer effect of tamoxifen, and the underlying mechanism involved in this combined effect in tamoxifen-sensitive (MCF-7) and tamoxifen-resistant (MCF-7/TAM) cells using MTS, flow cytometry and western blot assays. The results indicated that berberine demonstrated dose‑ and time‑dependent anti‑proliferative activity in MCF‑7 and MCF‑7/TAM cells. Furthermore, the combination of berberine and tamoxifen induced cell growth inhibition more effectively than tamoxifen alone. The present study also demonstrated that combinational treatment is more effective in inducing G1 phase arrest and activating apoptosis compared tamoxifen alone, which may be due to upregulation of P21 expression and downregulation of the B‑cell CLL/lymphoma 2(Bcl‑2)/Bcl‑2 associated X protein ratio. The results of the present study suggested that berberine may potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen, which will be useful for anti‑tumor therapy and further research.

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Apoptosis / drug effects
  • Berberine / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Synergism
  • Female
  • Humans
  • MCF-7 Cells
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tamoxifen / pharmacology*
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents, Hormonal
  • Cyclin-Dependent Kinase Inhibitor p21
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Tamoxifen
  • Berberine
  • Cyclin D1