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

Abstract:

: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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Duncan KL,Duncan MD,Alley MC,Sausville EA

doi

10.1016/s0006-2952(96)00557-6

subject

Has Abstract

pub_date

1996-11-22 00:00:00

pages

1553-60

issue

10

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(96)00557-6

journal_volume

52

pub_type

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