Magnetic nanoparticle-mediated gene therapy to induce Fas apoptosis pathway in breast cancer

Basoglu H., Goncu B., AKBAŞ F.

CANCER GENE THERAPY, vol.25, pp.141-147, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25
  • Publication Date: 2018
  • Doi Number: 10.1038/s41417-018-0017-2
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.141-147
  • Karadeniz Technical University Affiliated: No


CD95 (Fas) is a complex integral protein that can be expressed in many cells. It induces apoptosis when interacted with its ligand CD95L (FasL). However, cancer cells are resistant to CD95-induced apoptosis because of the changes in death domain (DD) of CD95 (procaspase-8 and c-Flip). In this study, magnetic nanoparticles and lipid-based gene transfection methods were performed to provide active Fas expression in breast cancer cells. Plasmid DNA (pDNA), which can express both human Fas and GFP, was transfected to MCF-7 breast cancer cells. Expression of c-FLIP and caspase-8 and effect of monoclonal antibody FasL for apoptosis stimulation were investigated. Also transfection success of methods and effects on surface protein were compared. Western blot results indicated that MCF-7 cells do not express caspase-8 but express large amount of c-FLIPL. Both lipid-based and magnetic nanoparticle-mediated gene transfection methods successfully applied. Caspase-8 apoptosis pathway was activated on transfected cells. Magnetic nanoparticle-mediated gene transfer is a successful non-viral method for transfection, and it does not affect the expression of other cell proteins, such as beta actin and lamin-B1. The raised c-FLIPL concentration in cytosol inhibits apoptosis. However, transfection of CD95-GFP-tagged pDNA significantly increases apoptosis by activating caspase-8 pathway. FasL interaction indicated a slight increase of apoptosis in the transfected cells. The method and pDNA applied in this study have potentials to be used in gene therapy for breast cancer.