Decreased mitochondrial membrane potential is an indicator of radioresistant cancer cells

Yoshikazu Kuwahara, Kazuo Tomita, Mehryar Habibi Roudkenar, Amaneh Mohammadi Roushandeh, Yusuke Urushihara, Kento Igarashi, Akihiro Kurimasa, Tomoaki Sato

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: To overcome radioresistant cancer cells, clinically relevant radioresistant (CRR) cells were established. To maintain their radioresistance, CRR cells were exposed 2 Gy/day of X-rays daily (maintenance irradiation: MI). To understand whether the radioresistance induced by X-rays was reversible or irreversible, the difference between CRR cells and those without MI for a year (CRR-NoIR cells) was investigated by the mitochondrial function as an index. Main methods: Radiation sensitivity was determined by modified high density survival assay. Mitochondrial membrane potential (Δψm) was determined by 5,5′,6,6′-tetrachloro-1,1′, tetraethylbenzimidazolocarbo-cyanine iodide (JC-1) staining. Rapid Glucose-Galactose assay was performed to determine the shift in their energy metabolism from aerobic glycolysis to oxidative phosphorylation in CRR cells. Involvement of prohibitin-1 (PHB1) in Δψm was evaluated by knockdown of PHB1 gene followed by real-time PCR. Key findings: CRR cells that exhibited resistant to 2 Gy/day X-ray lost their radioresistance after more than one year of culture without MI for a year. In addition, CRR cells lost their radioresistance when the mitochondria were activated by galactose. Furthermore, Δψm were increased and PHB1 expression was down-regulated, in the process of losing their radioresistance. Significance: Our finding reveled that tune regulation of mitochondrial function is implicated in radioresistance phenotype of cancer cells. Moreover, as our findings indicate, though further studies are required to clarify the precise mechanisms underlying cancer cell radioresistance, radioresistant cells induced by irradiation and cancer stem cells that are originally radioresistant should be considered separately, the radioresistance of CRR cells is reversible.

Original languageEnglish
Article number120051
JournalLife Sciences
Volume286
DOIs
Publication statusPublished - 2021 Dec 1

Keywords

  • Glycolysis
  • Hydrogen peroxide
  • Membrane potential
  • Mitochondria
  • Prohibitin
  • Radioresistance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint

Dive into the research topics of 'Decreased mitochondrial membrane potential is an indicator of radioresistant cancer cells'. Together they form a unique fingerprint.

Cite this