The natural product cucurbitacin e inhibits depolymerization of actin filaments

Pia M. Sörensen, Roxana E. Iacob, Marco Fritzsche, John R. Engen, William M. Brieher, Guillaume Charras, Ulrike S. Eggert

Research output: Contribution to journalArticlepeer-review


Although small molecule actin modulators have been widely used as research tools, only one cell-permeable small molecule inhibitor of actin depolymerization (jasplakinolide) is commercially available. We report that the natural product cucurbitacin E inhibits actin depolymerization and show that its mechanism of action is different from jasplakinolide. In assays using pure fluorescently labeled actin, cucurbitacin E specifically affects depolymerization without affecting polymerization. It inhibits actin depolymerization at substoichiometric concentrations up to 1:6 cucurbitacin E:actin. Cucurbitacin E specifically binds to filamentous actin (F-actin) forming a covalent bond at residue Cys257, but not to monomeric actin (G-actin). On the basis of its compatibility with phalloidin staining, we show that cucurbitacin E occupies a different binding site on actin filaments. Using loss of fluorescence after localized photoactivation, we found that cucurbitacin E inhibits actin depolymerization in live cells. Cucurbitacin E is a widely available plant-derived natural product, making it a useful tool to study actin dynamics in cells and actin-based processes such as cytokinesis.

Original languageEnglish (US)
Pages (from-to)1502-1508
Number of pages7
JournalACS chemical biology
Issue number9
StatePublished - Sep 21 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


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