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dc.contributor.authorHodeify, Rawad
dc.contributor.authorSiddiqui, Shoib Sarwar
dc.contributor.authorMatar, Rachel
dc.contributor.authorVazhappilly, Cijo George
dc.contributor.authorMerheb, Maxime
dc.contributor.authorAl Zouabi, Hussain
dc.contributor.authorMarton, John
dc.date.accessioned2021-02-15T11:00:02Z
dc.date.available2021-02-15T11:00:02Z
dc.date.issued2021-01-22
dc.identifier.citationHodeify , R , Siddiqui , S S , Matar , R , Vazhappilly , C G , Merheb , M , Al Zouabi , H & Marton , J 2021 , ' Modulation of calcium-binding proteins expression and cisplatin chemosensitivity by calcium chelation in human breast cancer MCF-7 cells ' , Heliyon , vol. 7 , no. 1 , e06041 . https://doi.org/10.1016/j.heliyon.2021.e06041
dc.identifier.issn2405-8440
dc.identifier.otherPubMedCentral: PMC7829211
dc.identifier.urihttp://hdl.handle.net/2299/23907
dc.description© 2021 The Author(s).
dc.description.abstractCisplatin (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.en
dc.format.extent2262050
dc.language.isoeng
dc.relation.ispartofHeliyon
dc.subjectBAPTA-AM
dc.subjectCalcium-binding proteins
dc.subjectCisplatin
dc.subjectIntracellular calcium
dc.subjectGeneral
dc.titleModulation of calcium-binding proteins expression and cisplatin chemosensitivity by calcium chelation in human breast cancer MCF-7 cellsen
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionCentre for Research in Mechanisms of Disease and Drug Discovery
dc.contributor.institutionCentre for Future Societies Research
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85099642180&partnerID=8YFLogxK
rioxxterms.versionofrecord10.1016/j.heliyon.2021.e06041
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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