Effect of an aryl chloroethyl urea on tubulin and vimentin syntheses in a human breast cancer cell line.
A new class of antineoplastic agents, 1-aryl-3-(2-chloroethyl) ureas (CEUs), was recently developed in our laboratory. To optimize the pharmacological and the biological properties of this new class of compounds and to determine its mechanism of action, at the cellular level, we studied the effect of 4-tert-butyl-[3-(2-chloroethyl) ureido] benzene (tBCEU) on MDA-MB-231, a human breast cancer hormone-independent cell line. The effect of tBCEU on protein synthesis and on the accumulation of specific mRNAs was evaluated. The results indicate that tBCEU increases the synthesis of at least two proteins present in the cytoskeleton: tubulin and vimentin. The effect of tBCEU on their transcripts indicates that tBCEU decreases the accumulation of tubulin and vimentin mRNA. These results suggest that the antineoplastic activity of tBCEU is in part related to an alteration in the synthesis pathway of tubulin and vimentin.
Poyet
P
P
Centre de Recherche, Hôpital Saint-François d'Assise, Québec, Canada.
Ritchot
N
N
Béchard
P
P
Gaudreáult
R C
RC
D001943:Breast Neoplasms / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014404:Tubulin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000096:biosynthesis*
D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014404:Tubulin; D014746:Vimentin; C084239:4-tert-butyl-(3-(2-chloroethyl)ureido)benzene