Cucurbitacins: elucidation of their interactions with the cytoskeleton

PeerJ

article

Xiaojuan Wang¹  Mine Tanaka¹  Herbenya Silva Peixoto¹  Michael Wink¹ 

[1] Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg

关键词: Cucurbitacins;    Cucurbitaceae;    Cytotoxicity;    Actin filament;    Microtubule;   

DOI  :  10.7717/peerj.3357

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY