TY - JOUR T1 - 2-Cyano-3,12-dioxooleana-1,9(11)-diene-28-oic Acid Disrupts Microtubule Polymerization: A Possible Mechanism Contributing to Apoptosis JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1158 LP - 1165 DO - 10.1124/mol.105.018572 VL - 69 IS - 4 AU - Robin D. Couch AU - Neil J. Ganem AU - Ming Zhou AU - Veljko M. Popov AU - Tadashi Honda AU - Timothy D. Veenstra AU - Michael B. Sporn AU - Amy C. Anderson Y1 - 2006/04/01 UR - http://molpharm.aspetjournals.org/content/69/4/1158.abstract N2 - 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 ∼7 μM, and to disrupt microtubules both in vivo and in vitro. CDDO inhibits tubulin polymerization in vitro, possibly through interactions with a hydrophobic site on β-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. ER -