title: Nuclear accumulation of anthracyclines in the endothelium studied by bimodal imaging: fluorescence and Raman microscopy.
abstract: Anthracycline antibiotics display genotoxic activity towards cancer cells but their clinical utility is limited by their cardiac and vascular toxicity. The aim of this study was to develop a Raman-based methodology to study the nuclear accumulation of anthracyclines in the endothelium. For this purpose bimodal confocal Raman and fluorescence imaging was used to monitor cellular composition changes as a result of anthracycline exposure on endothelial cells (EA.hy926), and nuclear drug accumulation, respectively. Simultaneously effects of anthracyclines on endothelium viability were investigated by caspases-3 and -7 and MTT assays. We demonstrated that nuclear accumulation of DOX and EDOX was similar; however, EDNR accumulated in endothelial nuclei at concentrations 10 times higher than DNR. In turn, epimers of DOX or DNR were both consistently less toxic on the endothelium as compared to their congeners as evidenced by MTT and caspase assays. In summary, bimodal Raman and fluorescence-based nucleus profiling proves to be a valuable tool to study structure-activity relationship of nuclear accumulation and toxicity of anthracyclines in endothelium.
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Majzner
authors.forename: T
authors.initials: T
authors.lastname: Wojcik
authors.forename: E
authors.initials: E
authors.lastname: Szafraniec
authors.forename: M
authors.initials: M
authors.lastname: Lukawska
authors.forename: I
authors.initials: I
authors.lastname: Oszczapowicz
authors.forename: S
authors.initials: S
authors.lastname: Chlopicki
authors.forename: M
authors.initials: M
authors.lastname: Baranska
mesh_terms: D018943:Anthracyclines / Q000737:chemistry / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D008856:Microscopy, Fluorescence; D013059:Spectrum Analysis, Raman
chemical_list: D018943:Anthracyclines; D004317:Doxorubicin; D053148:Caspase 3; D053179:Caspase 7