title: Electron microscopy analysis of early localization of cisplatin in ovarian carcinoma cells.
abstract: Taking advantage of the electron-dense nature of platinum, in this study the authors used an electron microscopy approach to investigate the cellular localization of cisplatin in an ovarian carcinoma cell line. Platinum spots were detected in contact with the plasma membrane and the nuclear envelope as well as in the cytoplasm and nuclear matrices. Contact with the plasma membrane was through a single blunt contact or spanning through the membrane. No sequestration in intracellular vescicles was observed, thereby supporting that phagocytosis and receptor-mediated endocytosis were not occurring. A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin. The present data suggest that cisplatin rapidly accumulates in the cell through endocytosis-independent membrane translocation and are consistent with passive diffusion.
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Beretta
authors.forename: Sabina C
authors.initials: SC
authors.lastname: Righetti
authors.forename: Luciano
authors.initials: L
authors.lastname: Lombardi
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Paola
authors.initials: P
authors.lastname: Perego
mesh_terms: D020346:Aquaporins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002945:Cisplatin / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C109669:AQP9 protein, human; D020346:Aquaporins; D012334:RNA, Neoplasm; D002945:Cisplatin