Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human Breast Cancer Cells in Vitro through Mitochondria-Mediated Apoptosis

Biol Pharm Bull. 2017;40(8):1232-1239. doi: 10.1248/bpb.b17-00010.

Abstract

Breast cancer is one of the most lethal malignancies in the world. Oxymatrine is the major effective and toxic alkaloid component which is derived from the root of Sophora flavescens AIT, a traditional Chinese medicine which is widely distributed in Asia and the Pacific Islands. In the current research study, we investigated the effects and mechanisms of action of oxymatrine on breast cancer cells. We demonstrated that the viability and single cell proliferation capability of MCF-7 and MDA-MB-231, two breast cancer cell lines which are widely used in in vitro study, were significantly suppressed in a time- and concentration-dependent manner. Furthermore, the cell cycle of breast cancer cells treated with oxymatrine was arrested at the S-phase of the cell cycle. Oxymatrine also triggered apoptosis in breast cancer cells by modulating apoptosis-related proteins, such as cleaved Caspase-3, cleaved Caspase-9 and poly(ADP-ribose)polymerase (PARP). The remarkable reduction in the ratio of Bcl-2/Bax was also observed in oxymatrine treated breast cancer cells. In conclusion, our research demonstrated that oxymatrine plays a critical role in suppressing carcinogenesis of breast cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, which suggests a promising application of this drug in breast cancer therapy.

Keywords: apoptosis; breast cancer; cell cycle; oxymatrine.

MeSH terms

  • Alkaloids / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Quinolizines / pharmacology*

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Quinolizines
  • oxymatrine
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9