The Psychiatric Drug Lithium Increases DNA Damage and Decreases Cell Survival in MCF-7 and MDA-MB-231 Breast Cancer Cell Lines Expos ed to Ionizing Radiation

Abstract

Background: Breast cancer is the most common cancer among women. Radiation therapy is used for treating almost every stage of breast cancer. A strategy to reduce irradiation side effects and to decrease the recurrence of cancer is concurrent use of radiation and radiosensitizers. We studied the effect of the antimanic drug lithium on radiosensitivity of estrogen-receptor (ER)-positive MCF-7 and ER-negative, invasive, and radioresistant MDA-MB-231 breast cancer cell lines. Methods: MCF-7 and MDA-MB-231 breast cancer cell lines were treated with 30 mM and 20 mM concentrations of lithium chloride (LiCl), respectively. These concentrations were determined by MTT viability assay. Growth curves were depicted and comet assay was performed for control and LiCl-treated cells after exposure to X-ray. Total and phosphorylated inactive levels of glycogen synthase kinase-3beta (GSK-3β) protein were determined by ELISA assay for control and treated cells. Results: Treatment with LiCl decreased cell proliferation after exposure to X-ray as indicated by growth curves of MCF-7 and MDA-MB-231 cell lines within six days following radiation. Such treatment increased the amount of DNA damages represented by percent DNA in Tails of comets at 0, 1, 4, and even 24 hours after radiation in both studied cell lines. The amount of active GSK-3β was increased in LiCl-treated cells in ER-positive and ER-negative breast cancer cell lines. Conclusion: Treatment with LiCl that increased the active GSK-3β protein, increased DNA damages and decreased survival independent of estrogen receptor status in breast cancer cells exposed to ionizing radiation.

Poly-Unsaturated Fatty Acids (PUFAs) from Cunninghamella elegans Grown on Glycerol Induce Cell Death and Increase Intracellular Reactive Oxygen Species

“…Synergistic actions were documented; however, the IC 50 exhibited by LiCl alone was measured to be around 20 mM after 48 h of exposure [71]. Other groups, mainly focusing on hepatocellular carcinoma and breast cancer, came up with similar results [72][73][74][75][76][77]. Another study, testing LiCl, documented the suppression of the proliferation in the ameloblastoma cell line AM-1, using a dose of 1 mM [78].…”

Genetically predicted bipolar disorder is causally associated with an increased risk of breast cancer: a two-sample Mendelian randomization analysis

“…Simultaneously, with the published genetic data from the Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 controls), the two-sample MR analysis offers a means to evaluate the causality between BD and breast cancer, overall and among specific immunohistochemical type, greatly increasing the scope and statistical power of MR (12). Furthermore, we conducted additional MR analyses to investigate whether genetically predicted BD would be associated with common confounders and mediators of breast cancer risk, like smoking status, use of antipsychotics and so on, based on existing literature (13)(14)(15)(16).…”