Mitochondrial DNA Deficiency in Ovarian Cancer Cells and Cancer Stem Cell-like Properties

Anticancer Res. 2015 Jul;35(7):3743-53.

Abstract

Background: A low quantity of mitochondrial DNA (mtDNA) is a risk factor in a variety of tumor types. However, it is unclear how mtDNA reduction influences tumor behavior.

Material and methods: mtDNA-deficient ovarian cancer cells were established by ethidium bromide (EtBr) treatment with additive combination of pyruvate and uridine.

Results: The mtDNA-deficient cells had a low growth and colony-forming efficiency compared to the control cells. RNA sequencing revealed down-regulation of mitochondrion-related genes and up-regulation of genes related to cell proliferation and anti-apoptosis. The expression of genes involved in cancer metastasis, proliferation, angiogenesis, drug resistance and cancer cell stemness were also up-regulated. Intriguingly, cancer stem cell markers CD90 and CD117 were both up-regulated by EtBr dose-dependently in both cell lines.

Conclusion: MtDNA deficiency may induce ovarian cancer stem cell-like properties through different ways in vitro, therefore contributing to different tumor behaviors.

Keywords: CSCs; Mitochondrion; RT-PCR; anti-apoptosis; cancer cell proliferation; cancer stem cells; immunocytochemistry; mitochondrial DNA deficiency/dysfunction; stemness; transcriptome sequencing/RNA deep-sequencing; western blotting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA, Mitochondrial / genetics*
  • Down-Regulation / genetics
  • Female
  • Humans
  • Mitochondria / genetics
  • Neoplastic Stem Cells / pathology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Up-Regulation / genetics

Substances

  • DNA, Mitochondrial