Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells

Folia Histochem Cytobiol. 2009;47(5):S141-6. doi: 10.2478/v10042-009-0084-1.

Abstract

Four novel dinuclear platinum(II) complexes of formula [Pt2L4(berenil)2]Cl4 (Pt1-Pt4) where L is piperazine (Pt1), 4-picoline (Pt2), 3-picoline (Pt3) or isopropylamine (Pt4) were compared to cisplatin in respect to collagen biosynthesis, beta1- integrin receptor, IGF-I receptor, phosphorylated MAP-kinases (ERK1/ERK2 and p38), phosphorylated Akt kinase expression and appearance of apoptosis in MCF-7 breast cancer cells. It was found that Pt1-Pt4 were more active inhibitor of collagen biosynthesis than cisplatin. The expression of IGF-I and beta1 integrin receptor, as well as phosphorylated MAPK, (ERK1 and ERK2 and p38) was significantly increased in cells incubated for 24 h with 20 muM Pt1-Pt4 compared to the control, not treated cells. The phenomenon was related to the increase expresion of NFkappaB by Pt1-Pt4 as shown by Western immunoblot analysis. Experiments made with annexin V-FITC and detection of apoptosis by a fluorescent microscopy assay revealed that novel dinuclear platinum(II) complexes (Pt1-Pt4) inhibited the proliferation of MCF-7 breast cancer cells by increasing the number of apoptotic and necrotic cells.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Humans
  • MCF-7 Cells*
  • NF-kappa B / metabolism
  • Organoplatinum Compounds / therapeutic use
  • Platinum*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Organoplatinum Compounds
  • Platinum