Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast cancer MCF-7 cells and its molecular mechanism

Nat Prod Res. 2018 Feb;32(4):493-497. doi: 10.1080/14786419.2017.1315575. Epub 2017 Apr 17.

Abstract

Cinobufagin (CBF) is an active ingredient isolated from Venenum Bufonis extracted and dried from the secretory glands of Bufo gargarizans Cantor. The purpose of the study was to investigate the effects and underlying mechanisms of CBF on human breast cancer MCF-7 cells in vitro. Our results showed that CBF exhibited obvious cytotoxicity on MCF-7 cells in a dose- and time-dependent manner, as indicated by CCK-8 assays. Also, Hoechst 33258 staining and flow cytometry assays showed that CBF strongly induced MCF-7 cell apoptosis and G1 phase arrest. In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays. Taken together, our data confirm that CBF inhibits growth and triggers apoptosis of MCF-7 cells by affecting the expression of Bax and Bcl-2 in vitro.

Keywords: Bax; Bcl-2; Cinobufagin; MCF-7 cells; apoptosis; human breast cancer.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy
  • Bufanolides / administration & dosage
  • Bufanolides / chemistry
  • Bufanolides / pharmacology*
  • Cell Proliferation / drug effects
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Up-Regulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • Bufanolides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • chan su
  • cinobufagin