http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#Head http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#provenance http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#pubinfo http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_1 http://purl.obolibrary.org/obo/RO_0002204 http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=1784 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_33697 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_2 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=9606 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_1 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://resource.belframework.org/belframework/1.0/namespace/selventa-legacy-chemical-names/Suberoylanilide%20hydroxamic%20acid http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.w3.org/2000/01/rdf-schema#label a(SCHEM:"Suberoylanilide hydroxamic acid") -> r(HGNC:CDKN1A) http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#provenance http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_3 http://www.w3.org/ns/prov#value BACKGROUND: Suberoylanilide hydroxamic acid (SAHA) is a prototype of the newly developed, second-generation, hybrid polar compounds. It is a novel histone deacetylase inhibitor with high potency for inducing cell differentiation of cultured murine erythroleukemia cells. Studies with SAHA have primarily been performed with hematopoietic tumor cells. Here we extent these studies with SAHA to human breast cancer cell lines in an attempt to find better therapeutic agents for breast cancer treatment. MATERIALS AND METHODS: Human breast cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-435, as well as normal cells, including the normal breast epithelial cell line MCF-10A, and fibroblasts, were treated with SAHA. Cells assayed for cell survival by using trypan blue exclusion assay, colony formation assay, and cell cycle and apoptosis analysis. The effects of SAHA on cell cycle and apoptosis regulatory proteins were examined by Western blots analysis. The identification of additional target genes was carried out by differential display (DD) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SAHA inhibited clonogenic growth of MCF7, MDA-MB-231, and MDA-MB-435 breast cancer cells. These cells were more sensitive to SAHA-mediated cytotoxic effects than normal breast epithelial cells and fibroblasts. The cytotoxic effects of SAHA on breast cancer cells were manifested by G1 and G2/M cell cycle arrest and eventual apoptosis. The pan-caspase inhibitor, Z-VAD.fmk, blocked SAHA-induced cell death, DNA laddering, and cleavage of poly(ADP-ribose) polymerase, indicating the involvement of caspases in SAHA-mediated apoptosis. In addition, SAHA modulated cell cycle and apoptosis regulatory proteins. For example, cyclin-dependent kinase (CDK) inhibitors p21WAF1/Cip1 and p27Kip1 were induced, and retinoblastoma protein pRb was hypophosphorylated. Moreover, SAHA induced several genes associated with differentiation and/ or growth inhibition. These genes encode gelsolin, isopentenyl-diphosphate delta isomerase (IDI1), and 1,25-dihydroxyvitamin D-3 up-regulated protein 1 (VDUP1), the last two of which were identified by DD. Induction of these genes may contribute to SAHA-mediated pro-differentiating and antiproliferative effects. CONCLUSIONS: SAHA induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer cells, possibly by modulating cell cycle and apoptosis regulatory proteins, such as CDK inhibitors p21 and p27, pRb, and other differentiation and/or growth inhibition-associated genes, including gelsolin, IDI1 and VDUP1. This, together with the low toxicity in normal cells, suggests that SAHA might have therapeutic potential for the treatment of human breast cancers. http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11126200 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11126200 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#_3 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM#pubinfo http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://purl.org/dc/terms/created 2014-07-03T14:29:53.715+02:00 http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAUIbIU5ZqzvA93HeTfMK8FZMH2djr_CsWN8k1SEMlsZM http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234