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 inCell Vol. 162; no. 2; pp. 403 - 411
Main Authors Borowiak, Malgorzata, Nahaboo, Wallis, Reynders, Martin, Nekolla, Katharina, Jalinot, Pierre, Hasserodt, Jens, Rehberg, Markus, Delattre, Marie, Zahler, Stefan, Vollmar, Angelika, Trauner, Dirk, Thorn-Seshold, Oliver
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 16.07.2015
IOS Press
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Summary: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.
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ISSN:0092-8674
1097-4172
2211-3428
1097-4172
2211-3436
DOI:10.1016/j.cell.2015.06.049