Lithium chloride attenuates mitomycin C induced necrotic cell death in MDA-MB-231 breast cancer cells via HMGB1 and Bax signaling.

Title Lithium chloride attenuates mitomycin C induced necrotic cell death in MDA-MB-231 breast cancer cells via HMGB1 and Bax signaling.
Authors M. Razmi; A. Rabbani-Chadegani; F. Hashemi-Niasari; P. Ghadam
Journal J Trace Elem Med Biol
DOI 10.1016/j.jtemb.2018.03.011
Abstract

The clinical use of potent anticancer drug mitomycin C (MMC) has limited due to side effects and resistance of cancer cells. The aim of this study was to investigate whether lithium chloride (LiCl), as a mood stabilizer, can affect the sensitivity of MDA-MB-231 breast cancer cells to mitomycin C. The cells were exposed to various concentrations of mitomycin C alone and combined with LiCl and the viability determined by trypan blue and MTT assays. Proteins were analyzed by western blot and mRNA expression of HMGB1 MMP9 and Bcl-2 were analyzed by RT-PCR. Flow cytometry was used to determine the cell cycle arrest and percent of apoptotic and necrotic cells. Concentration of Bax assessed by ELISA. Exposure of the cells to mitomycin C revealed IC value of 20??M, whereas pretreatment of the cells with LiCl induced synergistic cytotoxicity and IC value declined to 5??M. LiCl combined with mitomycin C significantly down-regulated HMGB1, MMP9 and Bcl-2 gene expression but significantly increased the level of Bax protein. In addition, the content of HMGB1 in the nuclei decreased and pretreatment with LiCl reduced the content of HMGB1 release induced by MMC. LiCl increased mitomycin C-induced cell shrinkage and PARP fragmentation suggesting induction of apoptosis in these cells. LiCl prevented mitomycin C-induced necrosis and changed the cell death arrest at G2/M-phase. Taking all together, it is suggested that LiCl efficiently enhances mitomycin C-induced apoptosis and HMGB1, Bax and Bcl-2 expression may play a major role in this process, the findings that provide a new therapeutic strategy for LiCl in combination with mitomycin C.

Citation M. Razmi; A. Rabbani-Chadegani; F. Hashemi-Niasari; P. Ghadam.Lithium chloride attenuates mitomycin C induced necrotic cell death in MDA-MB-231 breast cancer cells via HMGB1 and Bax signaling.. J Trace Elem Med Biol. 2018;48:8796. doi:10.1016/j.jtemb.2018.03.011

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Chlorine

Chlorine is a Block P, Group 17, Period 3 element. Its electron configuration is [Ne]3s23p5. The chlorine atom has a covalent radius of 102±4 pm and its Van der Waals radius is 175 pm. Chlorine ModelIn its elemental form, chlorine is a yellow-green gas. Chlorine is the second lightest halogen after fluorine. It has the third highest electronegativity and the highest electron affinity of all elements, making it a strong oxidizing agent. It is rarely found by itself in nature. Chlorine was discovered and first isolated by Carl Wilhelm Scheele in 1774. It was first recognized as an element by Humphry Davy in 1808.

Lithium

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