Direct interaction of Cucurbitacin E isolated from Alsomitra macrocarpa to actin filament

Momma, Keiko; Masuzawa, Yuko; Nakai, N.; Chujo, Moeko; Murakami, Akira; Kioka, Noriyuki; Kiyama, Yasunori; Akita, Toru; Nagao, Masaya

doi:10.1007/s10616-007-9100-5

Cited by 28 publications

(27 citation statements)

References 19 publications

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“…In addition, cucurbitacin F induces the formation of actin aggregates in Drosophila K c167 cells [28], and cucurbitacin E induces the disruption of actin cytoskeleton in prostate carcinoma cells [26]. Cucurbitacin E has also been shown to interact directly with actin and consequently stabilizes the polymerized actin [29]. More recently, it has been reported that cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics [19].…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells

Zhang

Ouyang

et al. 2011

ABBS

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Cucurbitacin B (CuB), a triterpenoid compound isolated from Cucurbitaceae plants, has been reported as a promising anti-cancer agent, yet its action mechanism is still controversial. In this study, we explored the potential mechanism of CuB in murine B16F10 melanoma cells. Anti-proliferation and anti-invasion effects were assessed in cultured cells, and in vivo anti-tumor activity was evaluated in a murine subcutaneous melanoma model. Flow cytometry was adopted to analyze cell cycle distribution and reactive oxygen species (ROS) levels. Actin levels were determined by western blot analysis, and the profiles of differential expressed proteins were identified by a quantitative proteomic approach. The results showed that CuB exerted inhibitory effects on cell proliferation, colony formation, as well as migration and invasion potential of the melanoma cells. The growth of subcutaneous melanoma was significantly inhibited in mice treated with CuB when compared with control group. Furthermore, CuB treatment caused rapid cell membrane blebbing and deformation, and induced G 2 /M-phase arrest and formation of multiploid cells. Notably, the G-actin pool was rapidly depleted and actin aggregates were formed quickly after CuB treatment. A number of cytoskeleton-regulatory proteins were differentially regulated. Blockage of ROS production significantly reduced the G-actin depletion ability and the anti-tumor activity of CuB. These findings indicate that CuB induces rapid depletion of the G-actin pool through ROS-dependent actin aggregation in melanoma cells, which may at least partly account for its anti-tumor activity.

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Section: Discussionmentioning

confidence: 99%

Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells

Zhang

Ouyang

et al. 2011

ABBS

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“…Among them, cucurbitacins, triterpene steroids extracted mainly from the Cucurbitaceae plant family, have been studied for their antitumoral, anti-inflammatory, and antioxidant properties [ 36 – 40 ]. In particular, cucurbitacin E (CuE) has been reported to possess anti-inflammatory and antiproliferative properties [ 41 ], effects mediated by its action on the polymerisation of the actin cytoskeleton [ 42 – 45 ].…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin E Has Neuroprotective Properties and Autophagic Modulating Activities on Dopaminergic Neurons

Arel-Dubeau

Longpré

Bournival

et al. 2014

Oxidative Medicine and Cellular Longevity

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Natural molecules are under intensive study for their potential as preventive and/or adjuvant therapies for neurodegenerative disorders such as Parkinson's disease (PD). We evaluated the neuroprotective potential of cucurbitacin E (CuE), a tetracyclic triterpenoid phytosterol extracted from the Ecballium elaterium (Cucurbitaceae), using a known cellular model of PD, NGF-differentiated PC12. In our postmitotic experimental paradigm, neuronal cells were treated with the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+) to provoke significant cellular damage and apoptosis or with the potent N,N-diethyldithiocarbamate (DDC) to induce superoxide (O2 •−) production, and CuE was administered prior to and during the neurotoxic treatment. We measured cellular death and reactive oxygen species to evaluate the antioxidant and antiapoptotic properties of CuE. In addition, we analyzed cellular macroautophagy, a bulk degradation process involving the lysosomal pathway. CuE showed neuroprotective effects on MPP+-induced cell death. However, CuE failed to rescue neuronal cells from oxidative stress induced by MPP+ or DDC. Microscopy and western blot data show an intriguing involvement of CuE in maintaining lysosomal distribution and decreasing autophagy flux. Altogether, these data indicate that CuE decreases neuronal death and autophagic flux in a postmitotic cellular model of PD.

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“…Another study indicated that cucurbitacin E and I induce cofilin dephosphorylation (activation) in leukemia cells [Nakashima et al, ]. However, cucurbitacins E and I, which disrupt the actin cytoskeleton and dephosphorylate cofilin in mammalian cells, do not induce actin polymerization in Dictyostelium and in purified actin [Momma et al, ; Knecht et al, ]. Thus, the mechanism underlying the cucurbitacin‐induced disruption of actin cytoskeleton is not fully understood.…”

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confidence: 99%

Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on slingshot homolog 1-mediated cofilin hyperactivation

Zhang

Ouyang

et al. 2013

J. Cell. Biochem.

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Accumulating evidence indicates that cucurbitacin B (CuB), as well as other cucurbitacins, damages the actin cytoskeleton in a variety of cell types. However, the underlying mechanism of such an effect is not well understood. In this study, we showed that CuB rapidly induced actin aggregation followed by actin rod formation in melanoma cells. Cofilin, a critical regulator of actin dynamics, was dramatically dephosphorylated (i.e., activated) upon CuB treatment. Notably, the activated cofilin subsequently formed rod-like aggregates, which were highly colocalized with actin rods, indicating the formation of cofilin-actin rods. Cofilin knockdown significantly suppressed rod formation but did not prevent actin aggregation. Furthermore, knockdown of the cofilin phosphatase Slingshot homolog 1 (SSH1), but not chronophin (CIN), alleviated CuB-induced cofilin hyperactivation and cofilin-actin rod formation. The activity of Rho kinase and LIM kinase, two upstream regulators of cofilin activation, was downregulated after cofilin hyperactivation. Pretreatment with a thiol-containing reactive oxygen species (ROS) scavenger N-acetyl cysteine, but not other ROS inhibitors without thiol groups, suppressed CuB-induced actin aggregation, cofilin hyperactivation and cofilin-actin rod formation, suggesting that thiol oxidation might be involved in these processes. Taken together, our results demonstrated that CuB-induced formation of cofilin-actin rods was mediated by SSH1-dependent but CIN-independent cofilin hyperactivation.

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Direct interaction of Cucurbitacin E isolated from Alsomitra macrocarpa to actin filament

Cited by 28 publications

References 19 publications

Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells

Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells

Cucurbitacin E Has Neuroprotective Properties and Autophagic Modulating Activities on Dopaminergic Neurons

Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on slingshot homolog 1-mediated cofilin hyperactivation

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