Modulation of calcium-binding proteins expression and cisplatin chemosensitivity by calcium chelation in human breast cancer MCF-7 cells

Modulation of calcium-binding proteins expression and cisplatin chemosensitivity by calcium chelation in human breast cancer MCF-7 cells

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crystal beaded candle holder Cisplatin (CDDP) is currently one of the most effective FDA-approved treatments for breast cancer.Previous studies have shown that CDDP-induced cell death in human breast cancer (MCF-7) cells is associated with disruption of calcium homeostasis.However, whether the sensitivity of breast cancer cells to cisplatin is associated with dysregulation of the expression of calcium-binding proteins (CaBPs) remains unknown.In this study, we evaluated the effect of the intracellular calcium chelator (BAPTA-AM) on viability of MCF-7 cells in the presence of toxic and sub-toxic doses of cisplatin.Furthermore, this study assessed the expression of CaBPs, calmodulin, S100A8, and S100A14 in MCF-7 cells treated with cisplatin.

Cell viability was determined using MTT-based in vitro toxicity assay.Intracellular calcium imaging was done using Fluo-4 AM, a cell-permeant fluorescent calcium indicator.Expression of CaBPs was tested using real-time quantitative PCR.Exposure of cells to increasing amounts of CDDP correlated with increasing fluorescence of the intracellular calcium indicator, here Fluo-4 AM.Conversely, treating cells with cisplatin significantly decreased mRNA levels of calmodulin, S100A8, and S100A14.

Treatment of the cells with calcium chelator, BAPTA-AM, significantly enhanced the cytotoxic effects of sub-toxic dose of cisplatin.Our results indicated a statistically significant negative correlation between calmodulin, S100A8, and S100A14 expression and sensitivity of breast cancer cells to a sub-toxic dose of cisplatin.We propose that modulating the activity of calcium-binding proteins, calmodulin, S100A8, and S100A14, could be used to increase cisplatin efficacy, lowering its treatment dosage while maintaining its chemotherapeutic value.