Ovarian cancer cells cisplatin sensitization agents selected by mass cytometry target ABCC2 inhibition. (31st May 2018)

• Record Type: Journal Article
• Authors: Comsa, Elisabeta; Nguyen, Kim-Anh; Loghin, Felicia; Boumendjel, Ahcène; Peuchmaur, Marine; Andrieu, Thibault; Falson, Pierre
• Is Part Of: Future medicinal chemistry. Volume 10:Number 11(2018)
• Page Start: 1349
• Page End: 1360
• Publication Date: 2018-05-31
• Subjects: ABCC2 aurones -- cisplatin resistance -- cyTOF inhibitors -- mass cytometry -- multidrug resistance -- ovarian cancer; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2017-0308
• Languages: English
• ISSNs: 1756-8919

Abstract

Aim: Cisplatin resistance in ovarian cancer remains a complex problem as tumors frequently develop resistance against drugs, a mechanism sometimes mediated by ATP-Binding Cassette transporters. Our goal was to find compounds restricting their inhibition capacity to the cisplatin efflux mediated by ABCC2 pump, among previously identified inhibitors, derived from the 2- indolylmethylenebenzofuranones.Methodology & results: An original method setup allows direct quantitation of platinum by employing cyTOF mass cytometry. Among tested derivatives, some led to a full platinum accumulation and efficiently resensitized cisplatin-resistant A2780 cells to cisplatin while preserving most of the calcein efflux activity.Conclusion: CyTOF is therefore a powerful and promising method to quantify cisplatin accumulation that may be used in the clinical setting to improve and personalize cancer treatment.