Multifunctional antioxidant nanoliposome-mediated delivery of PTEN plasmids restore the expression of tumor suppressor protein and induce apoptosis in prostate cancer cells

J Biomed Mater Res A. 2018 Dec;106(12):3152-3164. doi: 10.1002/jbm.a.36510. Epub 2018 Sep 7.

Abstract

Prostate cancer is the second leading cause of cancer death in men and about one in nine will be diagnosed in his lifetime. Loss of PTEN has been considered as one of the major factors leading to the origin of prostate cancer through modulating PI3K/AKT signaling pathways. In this study, we have prepared a multifunctional antioxidant nanoliposome containing PTEN plasmid and cerium oxide nanoparticles (CeNPs). The efficient delivery of PTEN plasmid to human prostate cancer cells (PC-3) leads to restoration of the expression of lost PTEN protein in the cell cytoplasm. The delivered superoxide dismutase (SOD)-mimetic CeNPs were also found to decrease the cytoplasmic free radical levels in prostate cancer cells. The above two activities induced DNA fragmentation and micronucleus formation in prostate cancer cells. Furthermore, it was also found that these multifunctional antioxidant nanoliposomes inhibit the PI3K/AKT signaling pathway to negatively regulate the cell viability of prostate cancer cells. The mRNA expression pattern of other relevant proteins predominantly involved in cancer cell proliferation and apoptosis suggested that the high PTEN expression could control the synthesis of oncogenic proteins. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3152-3164, 2018.

Keywords: PTEN plasmid; cerium oxide nanoparticles; gene delivery; multifunctional nanoparticles; nanoliposomes; prostate cancer; tumor suppressor protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Apoptosis
  • Cerium / administration & dosage
  • Cerium / therapeutic use*
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy
  • Humans
  • Male
  • Nanoparticles / administration & dosage
  • Nanoparticles / therapeutic use*
  • PC-3 Cells
  • PTEN Phosphohydrolase / genetics*
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Plasmids / therapeutic use*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy*

Substances

  • Antioxidants
  • Cerium
  • ceric oxide
  • PTEN Phosphohydrolase
  • PTEN protein, human