title: Application of fluorescence microscopy for investigation of cellular distribution of dinuclear platinum anticancer drugs.
abstract: The dinuclear platinum complexes with aliphatic diamines [{cis-Pt(NH(3))(2)Cl}(2)(mu-H(2)N(CH(2))(6)NH(2))](NO(3))(2) (1,1/c,c) and [{trans-Pt(NH(3))(2)Cl}(2)(mu-H(2)N(CH(2))(4)NH(2))](NO(3))(2) (1,1/t,t), which are known to be highly active in vitro against several cancer cell lines, have been modified with a fluorogenic reporter (carboxyfluorescein diacetate, CFDA) and a hapten (dinitrophenyl, DNP). These labeled complexes have been designed for fluorescence microscopy investigation of cellular pathways of promising dinuclear platinum anticancer drugs and present the first example of labeling biologically active dinuclear platinum complexes with a fluorescent reporter. The modified compounds interact with a guanine model base similarly to the label-free parent complexes. The uptake of the complexes with a fluorescent label and the respective unlabeled complexes in the U2-OS human osteosarcoma cell line and its cisplatin-resistant derivative, U2-OS/Pt cell line has been investigated. Cellular processing of the CFDA- and DNP-modified dinuclear platinum complexes in U2-OS and U2-OS/Pt cells has been studied.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Ganna V
authors.initials: GV
authors.lastname: Kalayda
authors.forename: Guofang
authors.initials: G
authors.lastname: Zhang
authors.forename: Tsion
authors.initials: T
authors.lastname: Abraham
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Tanke
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005452:Fluoresceins / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008856:Microscopy, Fluorescence; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004136:Dinitrobenzenes; D005452:Fluoresceins; D009944:Organoplatinum Compounds; C503896:bis(diamminechloroplatinum(II))(mu-1,4-butanediamine); C503895:bis(diamminechloroplatinum(II))(mu-1,6-hexanediamine); C027780:carboxyfluoresceindiacetate; D006147:Guanine; C014542:9-ethylguanine; D002945:Cisplatin