Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma
CI-994 or N -acetyldinaline [4-(acetylamino)- N -(2-amino-phenyl) benzamide] is an antitumor cytostatic agent currently undergoing clinical trial. Although several changes in cellular metabolism induced by the drug have been characterized, the primary molecular mechanism of its antitumor activity ha...
Gespeichert in:
| Veröffentlicht in: | Molecular cancer therapeutics 2003-04, Vol.2 (4), p.401 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 4 |
| container_start_page | 401 |
| container_title | Molecular cancer therapeutics |
| container_volume | 2 |
| creator | Kraker, Alan J Mizzen, Craig A Hartl, Brian G Miin, Johnson Allis, C David Merriman, Ronald L |
| description | CI-994 or N -acetyldinaline [4-(acetylamino)- N -(2-amino-phenyl) benzamide] is an antitumor cytostatic agent currently undergoing clinical trial. Although several changes
in cellular metabolism induced by the drug have been characterized, the primary molecular mechanism of its antitumor activity
has been previously unknown. Here, we show that CI-994 is a histone deacetylase (HDAC) inhibitor that causes histone hyperacetylation
in living cells. In assays of isolated enzymes, CI-994 inhibited HDAC-1 and HDAC-2 in a concentration-dependent fashion but
had no effect on the activity of the prototypical histone acetyltransferase GCN5. Acetylated histone H3-specific Western blots
were used to monitor histone acetylation in HCT-8 colon carcinoma cells treated with CI-994 in vitro . CI-994 induced hyperacetylation of H3 in a time- and dose-dependent fashion. H3 hyperacetylation was detectable as early
as 30 min after the addition of CI-994 to cells. These data demonstrate that inhibition of HDAC is an early event in cells
treated with CI-994 and suggest that this inhibition is mechanistically related to the antitumor activity of this compound. |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_highw</sourceid><recordid>TN_cdi_pubmed_primary_12700284</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>12700284</sourcerecordid><originalsourceid>FETCH-LOGICAL-h238t-a0c676892c8db47dd0fe7694758e201b2d18bd560f6ef121e2f591950fb83b403</originalsourceid><addsrcrecordid>eNo1j1FLwzAUhYMobk7_guRJtodAkiZt-jiLWmHqy3wSKUlzYyNtOtoOqb_e6ubTPZz7cTjnBM2ZjBRRkonTPy1JwuJohi76_pNSplLOztGM8YRSrsQc1U-t3dd68G3ArcO574c2AF6XMIxH24z4TZDl0Wp8aFfkmSw5Wf9qsqsgjPUK30L4nr4W3rEPOM-2ROGsraeATHflRDb6Ep05XfdwdbwL9Hp_t81ysnl5eMzWG1LxSA1E0zJO4qlqqawRibXUQRKnIpEKOGWGW6aMlTF1MTjGGXAnU5ZK6oyKjKDRAl0fcnd704Atdp1vdDcW_7Mn4OYAVP6j-vIdFKUOJXQd9DCVrQpeiEJQFv0AZO9gwg</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><creator>Kraker, Alan J ; Mizzen, Craig A ; Hartl, Brian G ; Miin, Johnson ; Allis, C David ; Merriman, Ronald L</creator><creatorcontrib>Kraker, Alan J ; Mizzen, Craig A ; Hartl, Brian G ; Miin, Johnson ; Allis, C David ; Merriman, Ronald L</creatorcontrib><description>CI-994 or N -acetyldinaline [4-(acetylamino)- N -(2-amino-phenyl) benzamide] is an antitumor cytostatic agent currently undergoing clinical trial. Although several changes
in cellular metabolism induced by the drug have been characterized, the primary molecular mechanism of its antitumor activity
has been previously unknown. Here, we show that CI-994 is a histone deacetylase (HDAC) inhibitor that causes histone hyperacetylation
in living cells. In assays of isolated enzymes, CI-994 inhibited HDAC-1 and HDAC-2 in a concentration-dependent fashion but
had no effect on the activity of the prototypical histone acetyltransferase GCN5. Acetylated histone H3-specific Western blots
were used to monitor histone acetylation in HCT-8 colon carcinoma cells treated with CI-994 in vitro . CI-994 induced hyperacetylation of H3 in a time- and dose-dependent fashion. H3 hyperacetylation was detectable as early
as 30 min after the addition of CI-994 to cells. These data demonstrate that inhibition of HDAC is an early event in cells
treated with CI-994 and suggest that this inhibition is mechanistically related to the antitumor activity of this compound.</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>PMID: 12700284</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Acetylation ; Antineoplastic Agents - pharmacology ; Blotting, Western ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Colonic Neoplasms - drug therapy ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - pharmacology ; Histone Deacetylase Inhibitors ; Histones - chemistry ; Histones - metabolism ; Humans ; Inhibitory Concentration 50 ; Models, Chemical ; Phenylenediamines - pharmacology ; Precipitin Tests ; Time Factors</subject><ispartof>Molecular cancer therapeutics, 2003-04, Vol.2 (4), p.401</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12700284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kraker, Alan J</creatorcontrib><creatorcontrib>Mizzen, Craig A</creatorcontrib><creatorcontrib>Hartl, Brian G</creatorcontrib><creatorcontrib>Miin, Johnson</creatorcontrib><creatorcontrib>Allis, C David</creatorcontrib><creatorcontrib>Merriman, Ronald L</creatorcontrib><title>Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>CI-994 or N -acetyldinaline [4-(acetylamino)- N -(2-amino-phenyl) benzamide] is an antitumor cytostatic agent currently undergoing clinical trial. Although several changes
in cellular metabolism induced by the drug have been characterized, the primary molecular mechanism of its antitumor activity
has been previously unknown. Here, we show that CI-994 is a histone deacetylase (HDAC) inhibitor that causes histone hyperacetylation
in living cells. In assays of isolated enzymes, CI-994 inhibited HDAC-1 and HDAC-2 in a concentration-dependent fashion but
had no effect on the activity of the prototypical histone acetyltransferase GCN5. Acetylated histone H3-specific Western blots
were used to monitor histone acetylation in HCT-8 colon carcinoma cells treated with CI-994 in vitro . CI-994 induced hyperacetylation of H3 in a time- and dose-dependent fashion. H3 hyperacetylation was detectable as early
as 30 min after the addition of CI-994 to cells. These data demonstrate that inhibition of HDAC is an early event in cells
treated with CI-994 and suggest that this inhibition is mechanistically related to the antitumor activity of this compound.</description><subject>Acetylation</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Histone Deacetylase Inhibitors</subject><subject>Histones - chemistry</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Models, Chemical</subject><subject>Phenylenediamines - pharmacology</subject><subject>Precipitin Tests</subject><subject>Time Factors</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j1FLwzAUhYMobk7_guRJtodAkiZt-jiLWmHqy3wSKUlzYyNtOtoOqb_e6ubTPZz7cTjnBM2ZjBRRkonTPy1JwuJohi76_pNSplLOztGM8YRSrsQc1U-t3dd68G3ArcO574c2AF6XMIxH24z4TZDl0Wp8aFfkmSw5Wf9qsqsgjPUK30L4nr4W3rEPOM-2ROGsraeATHflRDb6Ep05XfdwdbwL9Hp_t81ysnl5eMzWG1LxSA1E0zJO4qlqqawRibXUQRKnIpEKOGWGW6aMlTF1MTjGGXAnU5ZK6oyKjKDRAl0fcnd704Atdp1vdDcW_7Mn4OYAVP6j-vIdFKUOJXQd9DCVrQpeiEJQFv0AZO9gwg</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Kraker, Alan J</creator><creator>Mizzen, Craig A</creator><creator>Hartl, Brian G</creator><creator>Miin, Johnson</creator><creator>Allis, C David</creator><creator>Merriman, Ronald L</creator><general>American Association for Cancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20030401</creationdate><title>Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma</title><author>Kraker, Alan J ; Mizzen, Craig A ; Hartl, Brian G ; Miin, Johnson ; Allis, C David ; Merriman, Ronald L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h238t-a0c676892c8db47dd0fe7694758e201b2d18bd560f6ef121e2f591950fb83b403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acetylation</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Histone Deacetylase Inhibitors</topic><topic>Histones - chemistry</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Models, Chemical</topic><topic>Phenylenediamines - pharmacology</topic><topic>Precipitin Tests</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kraker, Alan J</creatorcontrib><creatorcontrib>Mizzen, Craig A</creatorcontrib><creatorcontrib>Hartl, Brian G</creatorcontrib><creatorcontrib>Miin, Johnson</creatorcontrib><creatorcontrib>Allis, C David</creatorcontrib><creatorcontrib>Merriman, Ronald L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kraker, Alan J</au><au>Mizzen, Craig A</au><au>Hartl, Brian G</au><au>Miin, Johnson</au><au>Allis, C David</au><au>Merriman, Ronald L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>2</volume><issue>4</issue><spage>401</spage><pages>401-</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>CI-994 or N -acetyldinaline [4-(acetylamino)- N -(2-amino-phenyl) benzamide] is an antitumor cytostatic agent currently undergoing clinical trial. Although several changes
in cellular metabolism induced by the drug have been characterized, the primary molecular mechanism of its antitumor activity
has been previously unknown. Here, we show that CI-994 is a histone deacetylase (HDAC) inhibitor that causes histone hyperacetylation
in living cells. In assays of isolated enzymes, CI-994 inhibited HDAC-1 and HDAC-2 in a concentration-dependent fashion but
had no effect on the activity of the prototypical histone acetyltransferase GCN5. Acetylated histone H3-specific Western blots
were used to monitor histone acetylation in HCT-8 colon carcinoma cells treated with CI-994 in vitro . CI-994 induced hyperacetylation of H3 in a time- and dose-dependent fashion. H3 hyperacetylation was detectable as early
as 30 min after the addition of CI-994 to cells. These data demonstrate that inhibition of HDAC is an early event in cells
treated with CI-994 and suggest that this inhibition is mechanistically related to the antitumor activity of this compound.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>12700284</pmid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-7163 |
| ispartof | Molecular cancer therapeutics, 2003-04, Vol.2 (4), p.401 |
| issn | 1535-7163 1538-8514 |
| language | eng |
| recordid | cdi_pubmed_primary_12700284 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Acetylation Antineoplastic Agents - pharmacology Blotting, Western Cell Line, Tumor Cell Nucleus - metabolism Colonic Neoplasms - drug therapy Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Histone Deacetylase Inhibitors Histones - chemistry Histones - metabolism Humans Inhibitory Concentration 50 Models, Chemical Phenylenediamines - pharmacology Precipitin Tests Time Factors |
| title | Modulation of Histone Acetylation by [4-(Acetylamino)-N-(2-Amino-phenyl) Benzamide] in HCT-8 Colon Carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T06%3A58%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_highw&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Modulation%20of%20Histone%20Acetylation%20by%20%5B4-(Acetylamino)-N-(2-Amino-phenyl)%20Benzamide%5D%20in%20HCT-8%20Colon%20Carcinoma&rft.jtitle=Molecular%20cancer%20therapeutics&rft.au=Kraker,%20Alan%20J&rft.date=2003-04-01&rft.volume=2&rft.issue=4&rft.spage=401&rft.pages=401-&rft.issn=1535-7163&rft.eissn=1538-8514&rft_id=info:doi/&rft_dat=%3Cpubmed_highw%3E12700284%3C/pubmed_highw%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/12700284&rfr_iscdi=true |