Repurposing cephalosporin antibiotics as pro-senescent radiosensitizers

Oncotarget. 2016 Jun 7;7(23):33919-33. doi: 10.18632/oncotarget.8984.


Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with radiosensitizers. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust radiosensitization in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic radiosensitizers to enhance the therapeutic ratio of radiotherapy.

Keywords: cephalosporin; drug repurposing; radiosensitizer; reactive oxygen species; senescence.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Cell Proliferation / drug effects*
  • Cell Proliferation / radiation effects*
  • Cellular Senescence / drug effects*
  • Cellular Senescence / radiation effects*
  • Cephalosporins / pharmacology*
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Repositioning*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Tumor Burden / drug effects
  • Tumor Burden / radiation effects
  • Xenograft Model Antitumor Assays


  • Anti-Bacterial Agents
  • Cephalosporins
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species