title: Differential uptake and selective permeability of fusarochromanone (FC101), a novel membrane permeable anticancer naturally fluorescent compound in tumor and normal cells.
abstract: The differential accumulation of fluorescent molecules in tumorigenic versus normal cells is a well-reported phenomenon and is the basis for photodiagnostic therapy. Through the use of confocal microscopy, the kinetic uptake and accumulation of fusarochromanone (FC101) was determined in two lines of living tumorigenic cells of mesenchymal-epithelial origin and normal fibroblast cells. Like other fluorescent cationic molecules, FC101 showed increased accumulation in tumorigenic cells; however, unlike other molecules, it appeared to be accumulated in a time-dependent manner. Also, unlike traditional fluorescent cationic molecules, FC101, a potent inhibitor of cell growth, showed preferential inhibition of tumorigenic B-16 melanoma cells and MCF7 cells derived from breast cancer adenocarcinoma when compared to normal cardiac fibroblasts. Further analysis of FC101's physicochemical properties using both experimentally obtained and simulated values revealed the likelihood of membrane permeation and oral bioavailability of the compound. These physicochemical properties of FC101 were also used to predict its intracellular localization lending credence to data observed by confocal microscopy.
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, 337 Graduate Science Research Center, Columbia, SC 29208, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Furmanski
authors.forename: Didier
authors.initials: D
authors.lastname: Dréau
authors.forename: Roy E
authors.initials: RE
authors.lastname: Wuthier
authors.forename: John W
authors.initials: JW
authors.lastname: Fuseler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000737:chemistry / Q000493:pharmacokinetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D005456:Fluorescent Dyes; C054523:fusarochromanone