Antimanic drug sensitizes breast cancer cell line to ionizing radiation

Abstract

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 β-catenin protein. Western blot analysis indicated that the β-catenin protein level was decreased in LiCl-treated cells. LiCl increased glycogen synthase kinase-3β (GSK-3β) protein that is involved in β-catenin degradation. The results demonstrated that LiCl could radiosensitize T47D cells by decreasing DNA repair, partially through Mre11 repression. GSK-3β/β-catenin/Mre11 pathway might be the connection between LiCl treatment and the decreased DNA repair in T47D cells.

Lithium Modulates Autophagy in Esophageal and Colorectal Cancer Cells and Enhances the Efficacy of Therapeutic Agents In Vitro and In Vivo

“…Enhanced GSK-3β expression in colon carcinoma samples was associated with resistance to 5-FU and in vitro inhibition of GSK-3β abolished cell viability via necroptosis and reduced xenograft growth in vivo [ 41 ]. More recently, lithium has been shown to synergistically enhance the anticancer effects of gemcitabine in pancreatic ductal adenocarcinoma cells [ 42 ], ionizing radiation in breast cancer cells [ 43 ] and sorafenib in glioblastoma multiforme cells [ 44 ] through targeting of GSK-3β signaling and induction of apoptotic cell death. Other studies have also indicated that alone, lithium has cytotoxic effects via TNF-α and FasL-mediated apoptosis [ 45 , 46 ].…”

An Unusual Large Size Ductal Carcinoma in Situ in a Patient on Lithium Therapy: A Case Report With Literature Review

“…PI3 kinase and EGFR mutation may be predictors of response to lithium in breast cancer. 12 However, one study reported that it may increase the incidence of renal cancers. 13 Lithium has also been proven to be neuroprotectant in cancer patients and is known to reduce chemotherapy induced cardiotoxicity and peripheral neuropathy.…”