Format

Send to

Choose Destination
Cell. 2015 Jul 16;162(2):403-411. doi: 10.1016/j.cell.2015.06.049. Epub 2015 Jul 9.

Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death.

Author information

1
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.
2
Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
3
Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany.
4
Walter Brendel Centre of Experimental Medicine, 27 Marchioninistrasse, Ludwig-Maximilians-Universität, München, Munich 81377, Germany.
5
Laboratoire de Chimie, CNRS, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France.
6
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.
7
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.

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.

KEYWORDS:

cancer chemotherapy; combretastatin; microtubule dynamics; photopharmacology; tubulin polymerisation inhibitor

PMID:
26165941
DOI:
10.1016/j.cell.2015.06.049
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center