Cellular uptake and apoptotic potential of rhenium labeled magnetic protein cages in MDA-MB-231 cells

Environ Toxicol Pharmacol. 2018 Oct:63:127-134. doi: 10.1016/j.etap.2018.08.014. Epub 2018 Aug 25.

Abstract

188Re-magnetoferritin nanoparticles (NPs) provide an attractive platform for localized radiation therapy due to their magnetic targeting capability while enhancing contrast in magnetic resonans imaging (MRI) signals. In this study, cellular uptake, in vitro cytotoxicity, apoptotic potential of a non-radioactive isotope of rhenium in the form of 187Re-magnetoferritin NPs were evaluated in both human normal mammary epithelial and breast metastatic adenocarcinoma cell lines. The results showed that, NP administration into the cells is through receptor mediated endocytosis and cancer cells displayed significantly higher uptake and cytotoxicity compared to normal cells. IC50 values of nanoparticles were calculated as 0.96 mg/mL for cancer and 1.73 mg/mL for normal cells. Annexin V/ Propidium Iodide (PI) staining also showed that, NPs induced higher apoptotic rates in cancer cells compared to normal cells. Gene expression analyses confirming the results showed that, pro-apoptotic PUMA and BAX genes were significantly up-regulated while anti-apoptotic BCL-2 and SURVIVIN genes were down-regulated in cancer cells compared to normal cells. Overall, these in vitro results suggest that, 187Re-magnetoferritin NPs have a promising potential for cancer therapy and can be used for imaging and diagnostic purposes for breast cancer at concentrations lower than 0.96 mg/mL. At concentrations above 1 mg/mL, NPs induce apoptosis which can also be used for cancer treatments.

Keywords: Apoptosis; Breast cancer cell lines; Cytotoxicity; Magnetoferritin.

MeSH terms

  • Apoferritins / chemistry*
  • Apoptosis Regulatory Proteins / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Endocytosis
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Iron / chemistry*
  • Magnetite Nanoparticles / chemistry
  • Oxides / chemistry*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Radioisotopes / chemistry
  • Radioisotopes / pharmacology*
  • Rhenium / chemistry
  • Rhenium / pharmacology*
  • Survivin / genetics
  • bcl-2-Associated X Protein / genetics

Substances

  • Apoptosis Regulatory Proteins
  • BAX protein, human
  • BBC3 protein, human
  • BCL2 protein, human
  • BIRC5 protein, human
  • Magnetite Nanoparticles
  • Oxides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Radioisotopes
  • Survivin
  • bcl-2-Associated X Protein
  • magnetoferritin
  • Rhenium-188
  • Rhenium
  • Apoferritins
  • Iron