期刊
CHEM
卷 6, 期 6, 页码 1408-1419出版社
CELL PRESS
DOI: 10.1016/j.chempr.2020.03.004
关键词
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资金
- National Research Foundation of Korea (NRF) [2018R1A2A1A05020236, 2018R1A3B1052702]
- Basic Science Research Program of the NRF [2017R1D1A1B03032561, 2017R1D1A1B03030062]
- Ministry of Education
- NRF [2016H1D3A1938052, 2014H1A2A1020978]
- National Cancer Institute of the United States [RO1 CA68682, R15 CA232765]
- National Research Foundation of Korea [21A20131212485, 2018R1A2A1A05020236, 2017R1D1A1B03032561, 2017R1D1A1B03030062, 2014H1A2A1020978, 2016H1D3A1938052] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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