Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells
Open accessAbstract
Cucurbitacin E has been identified by an empiric screening strategy as a sterol with potent growth inhibitory activity in vitro directed against prostate carcinoma explants (IC50 of 7-50 nM in 2- to 6-day exposures). The mechanism of cucurbitacin cytoxicity has not been elucidated previously. In the present study, we observed that cucurbitacin E caused marked disruption of the actin cytoskeleton, and in a series of cucurbitacin analogues, anti-proliferative activity correlated directly with the disruption of the F-actin cytoskeleton. The distribution of vimentin was also altered in cells exposed to cucurbitacin E, as vimentin associated with drug-induced membrane blebs. The appearance of microtubules was unaffected. Western blot analysis of intracellular actin in cells exposed to cucurbitacins and quantitation of rhodamine-phalloidin binding support the hypothesis that cucurbitacin treatment leads to an inappropriate increase in the filamentous or polymerized actin fraction in prostate carcinoma cells. We conclude that cucurbitacins are potent disruptors of cytoskeletal integrity. Prostate carcinoma cells appear notably sensitive to growth inhibition by cucurbitacin E.
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Cucurbitacin E and I are less likely to be protective compounds since they appear to induce cell death in various cancers.
“Curbitacini E & I, are less likely to be protective compounds since they apear to induce cell death in various cancers29,30”
From Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans (2020) · cites this paper as [30]
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The natural product cucurbitacin E inhibits depolymerization of actin filaments
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- Authors
- Duncan, K. L. K., Duncan, M. D., Alley, M. C., & Sausville, E. A.
- Affiliations
- National Institutes of Health (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Duncan, Kimberly L.K.
- ORCID
- Duncan, Mark D.
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 1996-11
- Volume
- 52
- Issue
- 10
- Pages
- 1553-1560
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2018877148
- Cited by
- 151
- References
- 38
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 18
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical Pharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- cucurbitacin E, cucurbitacins, prostate cancer, actin cytoskeleton, vimentin, cytoskeleton disruption, F-actin polymerization, membrane blebs, microtubules, antiproliferative activity, drug cytotoxicity
- MeSH terms
- Actins, Antineoplastic Agents, Cell Compartmentation, Cell Division, Cytoskeleton, Drug Screening Assays, Antitumor, Humans, Male, Prostatic Neoplasms, Triterpenes, Tumor Cells, Cultured, Vimentin
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