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

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• 作者：Ekram M. Saleh
• 关键词：Topoisomerase IIα ; Etoposide ; Ionizing radiation ; Double ; strand breaks ; DNA repair ; FaDu cells
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：36
• 期：11
• 页码：8985-8992
• 全文大小：600 KB
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• 作者单位：Ekram M. Saleh (1)
  
  1. Clinical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Giza, Egypt
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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