Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of nonhomologous end joining

Heather J. Boeckman, Kelly S. Trego, John Turchi

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The combination of cisplatin and ionizing radiation (IR) treatment represents a common modality for treating a variety of cancers. These two agents provide considerable synergy during treatment, although the mechanism of this synergy remains largely undefined. We have investigated the mechanism of cisplatin sensitization to IR using a combination of in vitro and in vivo experiments. A clear synergistic interaction between cisplatin and IR is observed in cells proficient in nonhomologous end joining (NHEJ) catalyzed repair of DNA double-strand breaks (DSB). In contrast, no interaction between cisplatin and IR is observed in NHEJ-deficient cells. Reconstituted In vitro NHEJ assays revealed that a site-specific cisplatin-DNA lesion near the terminus results in complete abrogation of NHEJ catalyzed repair of the DSB. These data show that the cisplatin-IR synergistic interaction requires the DNA-dependent protein kinase-dependent NHEJ pathway for joining of DNA DSBs, and the presence of a cisplatin lesion on the DNA blocks this pathway. In the absence of a functional NHEJ pathway, although the cells are hypersensitive to IR, there is no synergistic interaction with cisplatin.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalMolecular Cancer Research
Volume3
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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Ionizing Radiation
Cisplatin
Neoplasms
DNA
DNA-Activated Protein Kinase
Double-Stranded DNA Breaks

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of nonhomologous end joining. / Boeckman, Heather J.; Trego, Kelly S.; Turchi, John.

In: Molecular Cancer Research, Vol. 3, No. 5, 05.2005, p. 277-285.

Research output: Contribution to journalArticle

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