Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin

Michael R. Bubb, Adrian M.J. Senderowicz, Edward A. Sausville, Kimberly L.K. Duncan, Edward D. Korn

Research output: Contribution to journalArticle

Abstract

Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge, Jaspis johnstoni, has both fungicidal and antiproliferative activity. We now report that this peptide is a potent inducer of actin polymerization in vitro. The peptide has a much greater effect on Mg2+-actin than on Ca2+-actin. Competitive binding studies using rhodamine-phalloidin suggest that jasplakinolide binds to F-actin competitively with phalloidin with a dissociation constant of approximately 15 nM. This compares favorably to the previously reported IC50 of 35 nM for the antiproliferative effect of jasplakinolide on PC3 prostate carcinoma cells. The binding curve suggests that nearest neighbor positive cooperativity influences the binding of jasplakinolide (and perhaps also phalloidin) to F-actin. These results imply that jasplakinolide may exert its cytotoxic effect in vivo by inducing actin polymerization and/or stabilizing pre-existing actin filaments.

Original languageEnglish (US)
Pages (from-to)14869-14871
Number of pages3
JournalJournal of Biological Chemistry
Volume269
Issue number21
StatePublished - May 27 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bubb, M. R., Senderowicz, A. M. J., Sausville, E. A., Duncan, K. L. K., & Korn, E. D. (1994). Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. Journal of Biological Chemistry, 269(21), 14869-14871.