Pharmaceutical Sciences Faculty Publications
2-Cyano-3,12-Dioxooleana-1,9(11)-Diene-28-Oic Acid Disrupts Microtubule Polymerization: A Possible Mechanism Contributing to Apoptosis
Document Type
Article
Publication Date
4-1-2006
Journal Title
Molecular Pharmacology
ISSN
0026-895X
Volume
69
Issue
4
First Page
1158
Last Page
1165
DOI
10.1124/mol.105.018572
PubMed ID
16407469
Abstract
The semisynthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) has several biological activities, including the induction of apoptosis in many cancer cell lines. To identify potential protein targets, immobilized biotinylated CDDO was used to screen the proteome of a human lymphoma cell line (U937) sensitive to CDDO-induced apoptosis. Tubulin was identified as one of several putative targets of CDDO. CDDO was shown to selectively bind to tubulin, with a dissociation constant of approximately 7 microM, and to disrupt microtubules both in vivo and in vitro. CDDO inhibits tubulin polymerization in vitro, possibly through interactions with a hydrophobic site on beta-tubulin. The CDDO-tubulin interaction may also involve a reversible 1,4-addition with a protein sulfhydryl group. Unlike other known spindle poisons, CDDO does not result in a temporal increase in the mitotic index. Rather, CDDO seems to initiate apoptosis early in M phase.
Keywords
Binding sites, biopolymers, microscopy, fluorescence, microtubules, mitosis, oleanolic acid, tubulin
Recommended Citation
Couch, Robin D.; Ganem, Neil J.; Zhou, Ming; Popov, Veljko M.; Honda, Tadashi; Veenstra, Timothy D.; Sporn, Michael B.; and Anderson, Amy C., "2-Cyano-3,12-Dioxooleana-1,9(11)-Diene-28-Oic Acid Disrupts Microtubule Polymerization: A Possible Mechanism Contributing to Apoptosis" (2006). Pharmaceutical Sciences Faculty Publications. 404.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/404