Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell-less mollusc

Timothy Turner, William H. Jackson, George R. Pettit, Alan Wells, Andrew Kraft

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

BACKGROUND. Dolastatin 10 is an anticancer peptide isolated from the sea hare, Dolabela auricularia, which is currently in phase I trials. METHODS. The effects of dolastatin 10 on the DU-145 human prostate cancer cell line were studied both in tissue culture and in athymic nude mice. In tissue culture, after dolastatin 10 treatment, cell cycle kinetics were measured using propidum iodide, apoptosis was estimated using the TUNEL assay, and tubulin architecture studied by direct immunofluorescence. RESULTS. At concentrations of 1 nM (IC50 = 0.5 nM), dolastatin 10 completely inhibited the growth in tissue culture of human prostate cancer DU-145 cells. Growth inhibition was correlated with the arrest of these cells in G2/M and α- tubulin depolymerization. In athymic mice at a dose of 5 μg every 4 days i.p., dolastatin 10 blocked the diaphragmatic invasion of DU-145 tumor cells. CONCLUSIONS. Dolastatin 10 is a novel marine-derived compound with activity in the treatment of human prostate cancer in animals. The mechanism of action of this agent involves tubulin depolymerization but not the induction of apoptosis.

Original languageEnglish (US)
Pages (from-to)175-181
Number of pages7
JournalProstate
Volume34
Issue number3
DOIs
StatePublished - Feb 15 1998
Externally publishedYes

Fingerprint

dolastatin 10
Mollusca
Prostatic Neoplasms
Peptides
Tubulin
Nude Mice
Therapeutics
Apoptosis
Hares
Direct Fluorescent Antibody Technique
In Situ Nick-End Labeling
Iodides
Growth
Oceans and Seas
Inhibitory Concentration 50
Cell Cycle

Keywords

  • Dolastatin 10
  • EGF receptor
  • Prostate cancer
  • Tubulin

ASJC Scopus subject areas

  • Urology

Cite this

Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell-less mollusc. / Turner, Timothy; Jackson, William H.; Pettit, George R.; Wells, Alan; Kraft, Andrew.

In: Prostate, Vol. 34, No. 3, 15.02.1998, p. 175-181.

Research output: Contribution to journalArticle

Turner, Timothy ; Jackson, William H. ; Pettit, George R. ; Wells, Alan ; Kraft, Andrew. / Treatment of human prostate cancer cells with dolastatin 10, a peptide isolated from a marine shell-less mollusc. In: Prostate. 1998 ; Vol. 34, No. 3. pp. 175-181.
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