title: Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death.
abstract: Small molecules that interfere with microtubule dynamics, such as Taxol and the Vinca alkaloids, are widely used in cell biology research and as clinical anticancer drugs. However, their activity cannot be restricted to specific target cells, which also causes severe side effects in chemotherapy. Here, we introduce the photostatins, inhibitors that can be switched on and off in vivo by visible light, to optically control microtubule dynamics. Photostatins modulate microtubule dynamics with a subsecond response time and control mitosis in living organisms with single-cell spatial precision. In longer-term applications in cell culture, photostatins are up to 250 times more cytotoxic when switched on with blue light than when kept in the dark. Therefore, photostatins are both valuable tools for cell biology, and are promising as a new class of precision chemotherapeutics whose toxicity may be spatiotemporally constrained using light.
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany; Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Borowiak
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
authors.forename: Wallis
authors.initials: W
authors.lastname: Nahaboo
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reynders
authors.affiliation: Walter Brendel Centre of Experimental Medicine, 27 Marchioninistrasse, Ludwig-Maximilians-Universität, München, Munich 81377, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Nekolla
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jalinot
authors.affiliation: Laboratoire de Chimie, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
authors.forename: Jens
authors.initials: J
authors.lastname: Hasserodt
authors.affiliation: Walter Brendel Centre of Experimental Medicine, 27 Marchioninistrasse, Ludwig-Maximilians-Universität, München, Munich 81377, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rehberg
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Delattre
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Vollmar
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany. Electronic address: dirk.trauner@cup.uni-muenchen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
authors.affiliation: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany; Laboratoire de Chimie, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France. Electronic address: oliver.thorn-seshold@cup.uni-muenchen.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Thorn-Seshold
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000737:chemistry* / Q000633:toxicity; D016923:Cell Death; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000737:chemistry; D006801:Humans; D008027:Light; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis; D058105:Polymerization; D013267:Stilbenes / Q000737:chemistry* / Q000633:toxicity
chemical_list: D050256:Antimitotic Agents; D013267:Stilbenes; C058728:fosbretabulin
keywords: cancer chemotherapy; combretastatin; microtubule dynamics; photopharmacology; tubulin polymerisation inhibitor