Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2010 Sep 3;285(36):27944-57. doi: 10.1074/jbc.M110.103036. Epub 2010 Jun 21.

Synthetic triterpenoids target the Arp2/3 complex and inhibit branched actin polymerization.

Author information

  • 1Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.

Abstract

Synthetic triterpenoids are anti-tumor agents that affect numerous cellular functions including apoptosis and growth inhibition. Here, we used mass spectrometric and protein array approaches and uncovered that triterpenoids associate with proteins of the actin cytoskeleton, including actin-related protein 3 (Arp3). Arp3, a subunit of the Arp2/3 complex, is involved in branched actin polymerization and the formation of lamellipodia. 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO)-Im and CDDO-Me were observed to 1) inhibit the localization of Arp3 and actin at the leading edge of cells, 2) abrogate cell polarity, and 3) inhibit Arp2/3-dependent branched actin polymerization. We confirmed our drug effects with siRNA targeting of Arp3 and observed a decrease in Rat2 cell migration. Taken together, our data suggest that synthetic triterpenoids target Arp3 and branched actin polymerization to inhibit cell migration.

PMID:
20566646
[PubMed - indexed for MEDLINE]
PMCID:
PMC2934661
Free PMC Article

Images from this publication.See all images (11)Free text

FIGURE 1.
FIGURE 2.
FIGURE 3.
FIGURE 4.
FIGURE 5.
FIGURE 6.
FIGURE 7.
FIGURE 8.
FIGURE 9.
FIGURE 10.
FIGURE 11.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk