Inhibitors of histone deacetylase suppress the growth of MCF-7 breast cancer cells.
Inhibitors of histone deacetylase are attracting increasing interest due to their influence on transcription, differentiation, and apoptosis. We have investigated two synthetic inhibitors 3 and 4 of histone deacetylase and the natural product inhibitor trichostatin A for their ability to suppress the growth of MCF-7 breast cancer cells and here present complete and improved synthetic procedures. The compounds show a dose dependent inhibition of growth with activities in the low micromolar and nanomolar range. Trichostatin shows cytocidal effects at 100 nM and still has activity comparable to cisplatin (0.5 microM) at 10 nM. Whereas the synthetic inhibitor 3 has cytocidal activity at 10 microM compound 4 shows a maximum of 40% growth suppression at that concentration.
Schmidt
K
K
Institut für Pharmazie der Freien Universität Berlin, Abteilung Pharmazeutische Chemie, Germany.
Gust
R
R
Jung
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001943:Breast Neoplasms / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A