Cucurbitacins: elucidation of their interactions with the cytoskeleton

Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and...

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Hauptverfasser: Wang, Xiaojuan (VerfasserIn) , Tanaka, Mine (VerfasserIn) , Peixoto, Herbenya (VerfasserIn) , Wink, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 30 May 2017
In: PeerJ
Year: 2017, Jahrgang: 5
ISSN:2167-8359
DOI:10.7717/peerj.3357
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.7717/peerj.3357
Verlag, Volltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452965/
Volltext
Verfasserangaben:Xiaojuan Wang, Mine Tanaka, Herbenya Silva Peixoto and Michael Wink

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520 |a Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and actin filaments were studied in living cells (Hela and U2OS) and in vitro using GFP markers, immunofluorescence staining and in vitro tubulin polymerization assay. Cucurbitacin B, E and I apparently affected microtubule structures in living cells and cucurbitacin E inhibited tubulin polymerization in vitro with IC50 value of 566.91 ± 113.5 µM. Cucurbitacin E did not affect the nucleation but inhibited the growth phase and steady state during microtubule assembly in vitro. In addition, cucurbitacin B, E and I all altered mitotic spindles and induced the cell cycle arrest at G2/M phase. Moreover, they all showed potent effects on actin cytoskeleton by affecting actin filaments through the depolymerization and aggregation. The interactions of cucubitacin B, E and I with microtubules and actin filaments present new insights into their modes of action. 
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