title: Monitoring subcellular biotransformation of N-L-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection.
abstract: Development of prodrugs is a promising alternative to address cytotoxicity and nonspecificity of common anticancer agents. N-L-leucyldoxorubicin (LeuDox) is a prodrug that is biotransformed to the anticancer drug doxorubicin (Dox) in the extracellular space; however, its biotransformation may also occur intracellularly in endocytic organelles. Such organelle-specific biotransformation is yet to be determined. In this study, magnetically enriched endocytic organelle fractions from human uterine sarcoma cells were treated with LeuDox. Micellar electrokinetic chromatography with laser-induced fluorescence detection (MEKC-LIF) was used to determine that 10% of LeuDox was biotransformed to Dox, accounting for ~43% of the biotransformation occurring in the post-nuclear fraction. This finding suggests that endocytic organelles also participate in the intracellular biotransformation of LeuDox to Dox.
authors.affiliation: Department of Chemistry, University of Minnesota Twin-Cities, 207 Pleasant St. SE, Minneapolis, MN, 55455-0431, USA.
authors.forename: Chad P
authors.initials: CP
authors.lastname: Satori
authors.forename: Brandon
authors.initials: B
authors.lastname: Meyer
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Arriaga
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001711:Biotransformation; D045744:Cell Line, Tumor; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000295:instrumentation / Q000379:methods*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D007834:Lasers; D015388:Organelles / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; C073409:N-leucyldoxorubicin; D004317:Doxorubicin