title: Iron-dependent lysosomal dysfunction mediated by a natural product hybrid.
abstract: Artesumycin is a fluorescent hybrid of the natural products marmycin A and artemisinin. It was designed to combine the lysosomotropic properties of the angucycline and the iron-reactive capacity of the endoperoxide to target the lysosomal compartment of cancer cells. Herein, we show that artesumycin inhibits cancer cell proliferation in an iron-dependent manner and chemically fragments in vitro in the presence of redox-active iron(ii). Visual detection of artesumycin by fluorescence microscopy provided substantial evidence that the small molecule selectively targets lysosomes. This original approach based on a fluorescent and iron-reactive probe represents a powerful strategy for initiating and, concomitantly, visualizing lysosomal dysfunction in human cells.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France.
authors.forename: A
authors.initials: A
authors.lastname: Mariani
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France and Institut Curie Research Center, Organic Synthesis and Cell Biology Group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. tatiana.caneque-cobo@curie.fr raphael.rodriguez@curie.fr.
authors.forename: T T
authors.initials: TT
authors.lastname: Mai
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France.
authors.forename: E
authors.initials: E
authors.lastname: Zacharioudakis
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France.
authors.forename: A
authors.initials: A
authors.lastname: Hienzsch
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France.
authors.forename: A
authors.initials: A
authors.lastname: Bartoli
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France and Institut Curie Research Center, Organic Synthesis and Cell Biology Group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. tatiana.caneque-cobo@curie.fr raphael.rodriguez@curie.fr.
authors.forename: T
authors.initials: T
authors.lastname: Cañeque
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, 1 Avenue de la Terrasse, 91198 Gif sur-Yvette, France and Institut Curie Research Center, Organic Synthesis and Cell Biology Group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. tatiana.caneque-cobo@curie.fr raphael.rodriguez@curie.fr.
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez
mesh_terms: D000880:Anthraquinones / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism*; D001688:Biological Products / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D013058:Mass Spectrometry
chemical_list: D000880:Anthraquinones; D037621:Artemisinins; D001688:Biological Products; C000622946:artesumycin; D007501:Iron