Tumor Biology

, Volume 36, Issue 11, pp 8985–8992 | Cite as

Inhibition of topoisomerase IIα sensitizes FaDu cells to ionizing radiation by diminishing DNA repair

Research Article

Abstract

Despite the high efficiency of ionizing radiation (IR) to inactivate malignant tumours in general, an appreciable number of individual patients cannot be cured by standard IR. Head and neck tumours are not likely to be cured even by high-dose radiotherapy or chemotherapy. Accordingly, combined therapy is one of the most applicable strategies. Topoisomerase IIα is a ubiquitous enzyme that removes knots and tangles from the genetic material by generating and subsequently resealing of transient double-strand breaks. Due to its unique mechanism of action, topoisomerase IIα is the target of many chemotherapeutic agents such as etoposide. The aim of the present study is to examine the effect of inhibiting topoisomerase IIα by etoposide on the response of squamous cell carcinoma to IR. Results of the present study demonstrated a radiosensitizing effect for the topoisomerase IIα inhibitor etoposide on exponentially growing squamous cell carcinoma (FaDu) cell line especially at low radiation doses. This effect was found to be due to inhibition, by etoposide, of the repair of radiation-induced DNA damage. Cell cycle studies showed that the concentration of etoposide that sensitized the cells to radiation had no effect on the distribution of cells at different phases of the cell cycle. Synchronization of FaDu cells in different cell cycle phases revealed that proliferating G1 and G2 cells are responsible for sensitization of cells at low doses of ionizing radiation. It might, therefore, be concluded that topoisomerase II enzyme may be involved in the repair of radiation-induced DNA damage and consequently its inhibition constitute a strategy for sensitizing tumour cells to ionizing radiation.

Keywords

Topoisomerase IIα Etoposide Ionizing radiation Double-strand breaks DNA repair FaDu cells 

Abbreviations

IR

Ionizing radiation

DSB

Double-strand break

HR

Homologous recombination

NHEJ

Non-homologous end joining

DMSO

Dimethyl sulfoxide

RT

Room temperature

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Clinical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer InstituteCairo UniversityGizaEgypt

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