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

Abstract

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, 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.

Study on inhibitory effects of AsA, ZnCl2, and BAPTA-AM on Cd2+-induced cell oxidative stress and cytotoxicity by scanning electrochemical microscopy (SECM) technology

“…To date, several studies have shown an interaction between Ca 2+ and ROS: 57,58 maintaining the normal Ca 2+ level of the cell is conducive to the stability of the redox state in the cell, consequently ensuring the normal operation of mitochondria and other organelles. 59…”

“…To date, several studies have shown an interaction between Ca 2+ and ROS: 57,58 maintaining the normal Ca 2+ level of the cell is conducive to the stability of the redox state in the cell, consequently ensuring the normal operation of mitochondria and other organelles. 59 Low concentrations of AsA, ZnCl 2 , and BAPTA-AM could inhibit the oxidative stress induced by Cd, restore cell viability, and alleviate the cytotoxicity of Cd (Fig. 9).…”

Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia

“…Similarly, lipid-regulating enzymes ANXA1, S100A8, and FABP5 are co-regulated in a network with ApoE and APP in response to sepsis [ 40 ]. The known calcium-binding proteins (CALML5, S100A8, S100A14) modulate cancer therapeutics and survival [ 41 , 42 ]. Several candidates, especially TXN, S100A8, ANXA1 and LGALS7 are strongly associated with oxygen radical processes, a key ferroptosis trigger.…”

Synergistic effects of combined cisplatin and Clinacanthus nutans extract on triple negative breast cancer cells

“… 68 , 96 This is interesting because gap junction communication plays an important role in calcium (Ca 2+ ) signaling whereas cisplatin uptake, along with its cytotoxicity and chemosensitivity, are dependent on the cytosolic calcium concentration. 97 This claim can be supported by the lower cisplatin and IC 50 concentrations required to exert significant anticancer activity in MDA-MB-231 and MDA-MB-468 cells apart from apoptotic induction and the limited metastatic ability via the upregulation of differentiation and the downregulation of CSC makers. However, the mechanisms by which oleamide can induce connexins to mediate cisplatin chemosensitivity remain unclear and need to be investigated further.…”