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...

Full description

Bibliographic Details
Main Authors: Xiaojuan Wang, Mine Tanaka, Herbenya Silva Peixoto, Michael Wink
Format: Article
Language:English
Published: PeerJ Inc. 2017-05-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/3357.pdf
_version_ 1797420593871585280
author Xiaojuan Wang
Mine Tanaka
Herbenya Silva Peixoto
Michael Wink
author_facet Xiaojuan Wang
Mine Tanaka
Herbenya Silva Peixoto
Michael Wink
author_sort Xiaojuan Wang
collection DOAJ
description 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.
first_indexed 2024-03-09T07:04:41Z
format Article
id doaj.art-f0d557afe44e4750bc66ddf1cfd7de4d
institution Directory Open Access Journal
issn 2167-8359
language English
last_indexed 2024-03-09T07:04:41Z
publishDate 2017-05-01
publisher PeerJ Inc.
record_format Article
series PeerJ
spelling doaj.art-f0d557afe44e4750bc66ddf1cfd7de4d2023-12-03T09:45:59ZengPeerJ Inc.PeerJ2167-83592017-05-015e335710.7717/peerj.3357Cucurbitacins: elucidation of their interactions with the cytoskeletonXiaojuan Wang0Mine Tanaka1Herbenya Silva Peixoto2Michael Wink3Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, GermanyInstitute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, GermanyInstitute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, GermanyInstitute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, GermanyCucurbitacins, 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.https://peerj.com/articles/3357.pdfCucurbitacinsCucurbitaceaeCytotoxicityActin filamentMicrotubule
spellingShingle Xiaojuan Wang
Mine Tanaka
Herbenya Silva Peixoto
Michael Wink
Cucurbitacins: elucidation of their interactions with the cytoskeleton
PeerJ
Cucurbitacins
Cucurbitaceae
Cytotoxicity
Actin filament
Microtubule
title Cucurbitacins: elucidation of their interactions with the cytoskeleton
title_full Cucurbitacins: elucidation of their interactions with the cytoskeleton
title_fullStr Cucurbitacins: elucidation of their interactions with the cytoskeleton
title_full_unstemmed Cucurbitacins: elucidation of their interactions with the cytoskeleton
title_short Cucurbitacins: elucidation of their interactions with the cytoskeleton
title_sort cucurbitacins elucidation of their interactions with the cytoskeleton
topic Cucurbitacins
Cucurbitaceae
Cytotoxicity
Actin filament
Microtubule
url https://peerj.com/articles/3357.pdf
work_keys_str_mv AT xiaojuanwang cucurbitacinselucidationoftheirinteractionswiththecytoskeleton
AT minetanaka cucurbitacinselucidationoftheirinteractionswiththecytoskeleton
AT herbenyasilvapeixoto cucurbitacinselucidationoftheirinteractionswiththecytoskeleton
AT michaelwink cucurbitacinselucidationoftheirinteractionswiththecytoskeleton