title: The histone deacetylase inhibitor LBH589 inhibits expression of mitotic genes causing G2/M arrest and cell death in head and neck squamous cell carcinoma cell lines.
abstract: Head and neck squamous cell carcinoma represents a complex set of neoplasms arising in diverse anatomical locations. The site and stage of the cancer determine whether patients will be treated with single or multi-modality therapy. The HDAC inhibitor LBH589 is effective in treating some haematological neoplasms and shows promise for certain epithelial neoplasms. As with other human cancer cell lines, LBH589 causes up-regulation of p21, G2/M cell cycle arrest, and cell death of human HNSCC cell lines, as measured using flow cytometry and cDNA microarrays. Global RNA expression studies following treatment of the HNSCC cell line FaDu with LBH589 reveal down-regulation of genes required for chromosome congression and segregation (SMC2L1), sister chromatid cohesion (DDX11), and kinetochore structure (CENP-A, CENP-F, and CENP-M); these LBH589-induced changes in gene expression coupled with the down-regulation of MYC and BIRC5 (survivin) provide a plausible explanation for the early mitotic arrest and cell death observed. When LBH589-induced changes in gene expression were compared with gene expression profiles of 41 primary HNSCC samples, many of the genes that were down-regulated by LBH589 showed increased expression in primary HNSCC, suggesting that some patients with HNSCC may respond to treatment with LBH589.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA. prystows@aecom.yu.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.forename: Alfred
authors.initials: A
authors.lastname: Adomako
authors.forename: Richard V
authors.initials: RV
authors.lastname: Smith
authors.forename: Nicole
authors.initials: N
authors.lastname: Kawachi
authors.forename: Wendy
authors.initials: W
authors.lastname: McKimpson
authors.forename: Peter
authors.initials: P
authors.lastname: Atadja
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Parish
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Childs
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016923:Cell Death; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000077767:Panobinostat
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat