Parthenolide and costunolide decrease detyrosinated tubulin without compromising the overall microtubule network. Immunofluorescence of six-hour drug treated (A) Bt-549 and (B) MDA-MB-157 stained for detyrosinated tubulin and α-tubulin show that parthenolide (Parth; 10 μM) and costunolide (Cost; 25 μM) decrease and disrupt filamentous detyrosinated tubulin (Detyr) while leaving the overall microtubule network intact (α-tub). Treatment with colchicine (Col; 50 μM) disrupts both detyrosinated and α-tubulin filaments. Taxol (Tax; 0.5 μg/ml) increases bundling and disrupts organization of detyrosinated and α-tubulin filaments. Resveratrol (ResV; 50 μg/ml) did not significantly affect detyrosinated or α-tubulin.