The redox status of human breast cancer cell lines (MCF-7 and MDA-MB231) treated with novel dinuclear berenil-platinum(II) complexes

Pharmazie. 2014 Dec;69(12):923-8.

Abstract

This study compared the effects of cisplatinum and novel berenil-platinum(ll) complexes on the redox status of breast cancer cells that were estrogen receptor-positive (MCF-7) or estrogen receptor-negative (MDA-MB231). Both cell lines were treated with cisplatinum or the following berenil-platinum(ll) complexes: Pt2(isopropylamine)4(berenil)2, Pt2(piperidine)4(berenil)2, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4-picoline)4(berenil)2. Changes in levels of reactive oxygen species, levels and activities of antioxidants, and lipid peroxidation products levels were measured. All investigated compounds enhanced ROS generation, reduced the activity of antioxidant enzymes (e.g., glutathione peroxidase and glutathione reductase), and decreased levels of small-molecule antioxidants (GSH, vitamins E and A). Such conditions are conducive to generating oxidative stress and phospholipids peroxidation. Cellular phospholipids in MCF-7 cells were most sensitive to the Pt2(isopropylamine)4(berenil)2 complex, whereas MDA-MB231 cells were not particularly sensitive to any berenil-platinum(ll) complex. These findings will facilitate future anticancer drug design strategy for breast cancer pharmacotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • DNA Methylation / drug effects
  • Diminazene / analogs & derivatives*
  • Diminazene / pharmacology
  • Female
  • Humans
  • Organoplatinum Compounds / pharmacology*
  • Oxidation-Reduction
  • Phospholipids / metabolism
  • Picolines / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Organoplatinum Compounds
  • Phospholipids
  • Picolines
  • Pt2(2-picoline)4(berenil)2
  • Reactive Oxygen Species
  • diminazene aceturate
  • Cisplatin
  • Diminazene