A novel schiff base zinc coordination compound inhibits proliferation and induces apoptosis of human osteosarcoma cells

J Huazhong Univ Sci Technolog Med Sci. 2015 Oct;35(5):700-706. doi: 10.1007/s11596-015-1493-3. Epub 2015 Oct 22.

Abstract

Various kinds of schiff base metal complexes have been proven to induce apoptosis of tumor cells. However, it remains largely unknown whether schiff base zinc complexes induce apoptosis in human cancer cells. Here, we synthesized a novel schiff base zinc coordination compound (SBZCC) and investigated its effects on the growth, proliferation and apoptosis of human osteosarcoma MG-63 cells. A novel SBZCC was synthesized by chemical processes and used to treat MG-63 cells. The cell viability was determined by CCK-8 assay. The cell cycle progression, mitochondrial membrane potential and apoptotic cells were analyzed by flow cytometry. The apoptosis-related proteins levels were determined by immunoblotting. Treatment of MG-63 cells with SBZCC resulted in inhibition of cell proliferation and cell cycle arrest at G1 phase. Moreover, SBZCC significantly reduced the mitochondrial membrane potential and induced apoptosis, accompanied with increased Bax/Bcl-2 and FlasL/Fas expression as well as caspase-3/8/9 cleavage. Our results demonstrated that the synthesized novel SBZCC could inhibit the proliferation and induce apoptosis of MG-63 cells via activating both the mitochondrial and cell death receptor apoptosis pathways, suggesting that SBZCC is a promising agent for the development as anticancer drugs.

Keywords: anti-tumor activity; apoptosis; bone sarcoma MG-63 cells; mitochondrial membrane potential; schiff base zinc coordination compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Schiff Bases / chemistry*
  • Signal Transduction
  • Zinc / chemistry*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • Coordination Complexes
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Schiff Bases
  • bcl-2-Associated X Protein
  • fas Receptor
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Zinc