Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death
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. He...
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Published in | Cell Vol. 162; no. 2; pp. 403 - 411 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
16.07.2015
IOS Press |
Subjects | |
Online Access | Get full text |
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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.
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•Photostatins (PSTs) switch microtubule dynamics off and on under blue and green light•PSTs modulate microtubule dynamics in live cells with response time below 1 s•PSTs control mitosis in vivo with spatial precision on the single-cell level•PSTs exposed to blue light are 250 times more cytotoxic than PSTs kept in the dark
Microtubule-inhibiting small molecules are crucial for cell biology research and in cancer therapy. Photostatins are microtubule inhibitors that can be switched on and off in vivo by visible light, modulating microtubule dynamics with subsecond response time, and controlling mitosis with single-cell spatial precision. Photostatins are also 250 times more cytotoxic under blue light than when kept in the dark, making them both valuable tools for cell biology, and promising as precision-targeted chemotherapeutics. |
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AbstractList | 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. 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. [Display omitted] •Photostatins (PSTs) switch microtubule dynamics off and on under blue and green light•PSTs modulate microtubule dynamics in live cells with response time below 1 s•PSTs control mitosis in vivo with spatial precision on the single-cell level•PSTs exposed to blue light are 250 times more cytotoxic than PSTs kept in the dark Microtubule-inhibiting small molecules are crucial for cell biology research and in cancer therapy. Photostatins are microtubule inhibitors that can be switched on and off in vivo by visible light, modulating microtubule dynamics with subsecond response time, and controlling mitosis with single-cell spatial precision. Photostatins are also 250 times more cytotoxic under blue light than when kept in the dark, making them both valuable tools for cell biology, and promising as precision-targeted chemotherapeutics. 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.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. |
Author | Reynders, Martin Jalinot, Pierre Delattre, Marie Rehberg, Markus Trauner, Dirk Thorn-Seshold, Oliver Nahaboo, Wallis Vollmar, Angelika Hasserodt, Jens Nekolla, Katharina Zahler, Stefan Borowiak, Malgorzata |
Author_xml | – sequence: 1 givenname: Malgorzata surname: Borowiak fullname: Borowiak, Malgorzata organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany – sequence: 2 givenname: Wallis surname: Nahaboo fullname: Nahaboo, Wallis organization: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d’Italie, 69364 Lyon, France – sequence: 3 givenname: Martin surname: Reynders fullname: Reynders, Martin organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany – sequence: 4 givenname: Katharina surname: Nekolla fullname: Nekolla, Katharina organization: Walter Brendel Centre of Experimental Medicine, 27 Marchioninistrasse, Ludwig-Maximilians-Universität, München, Munich 81377, Germany – sequence: 5 givenname: Pierre surname: Jalinot fullname: Jalinot, Pierre organization: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d’Italie, 69364 Lyon, France – sequence: 6 givenname: Jens surname: Hasserodt fullname: Hasserodt, Jens organization: Laboratoire de Chimie, CNRS, École Normale Supérieure de Lyon, 46 Allée d’Italie, 69364 Lyon, France – sequence: 7 givenname: Markus surname: Rehberg fullname: Rehberg, Markus organization: Walter Brendel Centre of Experimental Medicine, 27 Marchioninistrasse, Ludwig-Maximilians-Universität, München, Munich 81377, Germany – sequence: 8 givenname: Marie surname: Delattre fullname: Delattre, Marie organization: Laboratoire de Biologie Moléculaire de la Cellule, CNRS, École Normale Supérieure de Lyon, 46 Allée d’Italie, 69364 Lyon, France – sequence: 9 givenname: Stefan surname: Zahler fullname: Zahler, Stefan organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany – sequence: 10 givenname: Angelika surname: Vollmar fullname: Vollmar, Angelika organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany – sequence: 11 givenname: Dirk surname: Trauner fullname: Trauner, Dirk email: dirk.trauner@cup.uni-muenchen.de organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany – sequence: 12 givenname: Oliver surname: Thorn-Seshold fullname: Thorn-Seshold, Oliver email: oliver.thorn-seshold@cup.uni-muenchen.de organization: Department of Chemistry and Pharmacy and Centre for Integrated Protein Science, Ludwig-Maximilians-University Munich, 5-13 Butenandtstrasse, 81377 Munich, Germany |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26165941$$D View this record in MEDLINE/PubMed https://hal.science/hal-01234187$$DView record in HAL |
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Snippet | Small molecules that interfere with microtubule dynamics, such as Taxol and the Vinca alkaloids, are widely used in cell biology research and as clinical... |
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SubjectTerms | Animals Antimitotic Agents - chemistry Antimitotic Agents - toxicity cancer chemotherapy Cell Death Cell Line, Tumor Chemical Sciences combretastatin Cytoskeleton - chemistry Humans Light Mice microtubule dynamics Microtubules - drug effects Mitosis or physical chemistry photopharmacology Polymerization Stilbenes - chemistry Stilbenes - toxicity Theoretical and tubulin polymerisation inhibitor |
Title | Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death |
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