Abstract
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.
Highlights
Cucurbitacins are a class of cucurbitane-type tetracyclic triterpenoids that are mainly produced by plants of the family of Cucurbitaceae (Duncan et al, 1996; Kaushik, Aeri & Mir, 2015; Wink & Van Wyk, 2008)
We investigated the effects of cucurbitacin B, E and I on microtubules and actin filaments in living cells using GFP markers and immunofluorescence staining
Cucurbitacin B and E caused a higher toxicity than cucurbitacin I, which is close to the microtubule-binding agent colchicine
Summary
Cucurbitacins are a class of cucurbitane-type tetracyclic triterpenoids that are mainly produced by plants of the family of Cucurbitaceae (Duncan et al, 1996; Kaushik, Aeri & Mir, 2015; Wink & Van Wyk, 2008). Hundreds of cucurbitacins that occur in a diversity of plants share the same tetracyclic scaffold and can be divided into 12 main categories according to their substituents (Chen et al, 2012; Lee, Iwanski & Thoennissen, 2010). Cucurbitacins B and E (Fig. 1) have been identified to be the primary cucurbitacin types by plant secondary metabolism studies (Abbas et al, 2013; Gry, Søborg & Andersson, 2006; Kaushik, Aeri & Mir, 2015). Other cucurbitacin types could be generated by enzymatic reactions. Current studies have revealed several molecular targets of cucurbitacins such as JAK2/STAT3 pathway, cofilin, cyclins, cdc, COX-2, TYR and EcR, among which actin cytoskeleton appears to be an early target
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