Antitumor activity of SA12, a novel peptide, on SKBr-3 breast cancer cells via the mitochondrial apoptosis pathway

Drug Des Devel Ther. 2015 Mar 2:9:1319-30. doi: 10.2147/DDDT.S75780. eCollection 2015.

Abstract

Breast cancer is considered to be the most common malignancy in women. Treatment of breast cancer has been focused on molecular targeted therapy, and anticancer peptides are considered to be some of the most promising candidate drugs. In the current study, we used mRNA-peptide display technology to screen antibreast cancer peptides and identified a novel peptide, SA12, which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 breast cancer cells. The mechanism by which SA12 peptide triggers apoptosis was further investigated using a pull-down assay, reverse transcription-polymerase chain reaction, and Western blotting analysis. The results demonstrated that this peptide could interact with tumor-associated proteins MECP2 and CDC20B, which further induced apoptosis of tumor cells via the mitochondrial pathway involving the Bcl-2 family and related caspases. We propose that the novel SA12 peptide has the potential to provide a new strategy for the development of targeted therapy in breast cancer.

Keywords: Bcl-2; MECP2; caspase; mRNA display; targeted therapy.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • SA12 peptide