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

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.

• Publication year

  1996

• Venue

  Biochemical Pharmacology

• Publication date

  1996-11-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S0006-2952(96)00557-6PMID 8937470
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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