Antimanic drug sensitizes breast cancer cell line to ionizing radiation

作者：Rouhani Maryam; Goliaei Bahram^*; Khodagholi Fariba; Nikoofar Alireza

来源：General Physiology and Biophysics, 2014, 33(2): 235-242.

DOI：10.4149/gpb_gpb_2013080

• LiCl
• T47D
• Radiosensitivity
• DNA repair
• Mrel1

Breast cancer is one of the most prevalent types of cancer among women. Lithium chloride (LiCl) is an FDA-approved drug for bipolar disorder. Breast cancer is reported to occur with higher rate in women with bipolar disorder. The effect of LiCl on the response of breast cancer cells to ionizing radiation has not been studied. We studied the effect of LiCl on the radiosensitivity of radioresistant T47D breast cancer cell line. Treatment of T47D cells with 20 mM LiCl for 24 hours decreased the radioresistance of these cells indicated by clonogenic survival assay. Comet assay demonstrated decreased DNA repair in LiCl-treated cells. LiCl treatment also decreased the meiotic recombination 11 (Mre11) mRNA level. Mre11 is an essential protein for DNA repair whose transcription is regulated by beta-catenin protein. Western blot analysis indicated that the beta-catenin protein level was decreased in LiCl-treated cells. LiCl increased glycogen synthase kinase-3 beta (GSK-3 beta) protein that is involved in beta-catenin degradation. The results demonstrated that LiCl could radiosensitize T47D cells by decreasing DNA repair, partially through Mre11 repression. GSK-3 beta/beta-catenin/Mre11 pathway might be the connection between LiCl treatment and the decreased DNA repair in T47D cells.

• 出版日期2014