Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells

Kimberly L.K. Duncan, Mark D. Duncan, Michael C. Alley, Edward A. Sausville

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Cucurbitacin E has been identified by an empiric screening strategy as a sterol with potent growth inhibitory activity in vitro directed against prostare 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.

Original languageEnglish (US)
Pages (from-to)1553-1560
Number of pages8
JournalBiochemical Pharmacology
Volume52
Issue number10
DOIs
StatePublished - Nov 22 1996
Externally publishedYes

Keywords

  • actin
  • cytoskeleton
  • prostate neoplasm drug treatment
  • steroid
  • vimentin

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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