Mitochondrial Relocation of a Common Synthetic Antibiotic: A Non-genotoxic Approach to Cancer Therapy

Kyoung Sunwoo, Miae Won, Kyung Phil Ko, Miri Choi, Jonathan F. Arambula, Sung Gil Chi, Jonathan L. Sessler, Peter Verwilst, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Tumor recurrence as a result of therapy-induced nuclear DNA lesions is a major issue in cancer treatment. Currently, only a few examples of potentially non-genotoxic drugs have been reported. Mitochondrial re-localization of ciprofloxacin, one of the most commonly prescribed synthetic antibiotics, is reported here as a new approach. Conjugation of ciprofloxacin to a triphenyl phosphonium group (giving lead Mt-CFX) is used to enhance the concentration of ciprofloxacin in the mitochondria of cancer cells. The localization of Mt-CFX to the mitochondria induces oxidative damage to proteins, mtDNA, and lipids. A large bias in favor of mtDNA damage over nDNA was seen with Mt-CFX, contrary to classic cancer chemotherapeutics. Mt-CFX was found to reduce cancer growth in a xenograft mouse model and proved to be well tolerated. Mitochondrial re-localization of antibiotics could emerge as a useful approach to generating anticancer leads that promote cell death via the selective induction of mitochondrially mediated oxidative damage.

Original languageEnglish
Pages (from-to)1408-1419
Number of pages12
JournalChem
Volume6
Issue number6
DOIs
Publication statusPublished - 2020 Jun 11

Keywords

  • DNA damage
  • SDG3: Good health and well-being
  • ciprofloxacin
  • mitochondria
  • non-genotoxic cancer therapy
  • prodrug
  • reactive oxygen species
  • targeted therapeutics

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Biochemistry, medical
  • Materials Chemistry

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