Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents
Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and Z...
Gespeichert in:
| Veröffentlicht in: | Molecular and cellular biology 2014-07, Vol.34 (13), p.2382-2395 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2395 |
|---|---|
| container_issue | 13 |
| container_start_page | 2382 |
| container_title | Molecular and cellular biology |
| container_volume | 34 |
| creator | Jutooru, Indira Guthrie, Aaron S. Chadalapaka, Gayathri Pathi, Satya Kim, KyoungHyun Burghardt, Robert Jin, Un-Ho Safe, Stephen |
| description | Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced apoptosis and decreased pancreatic cancer cell growth and invasion, indicating that downregulation of Sp transcription factors is an important common mechanism of action for PEITC and other ROS-inducing anticancer agents. |
| doi_str_mv | 10.1128/MCB.01602-13 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmed_primary_24732804</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>24732804</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-43fede14627c5520c5a47f5ad519202b90a1d4383eca096c13ef3e6375b8de9a3</originalsourceid><addsrcrecordid>eNptkFtLJDEQRoO4eH_zWfoH2G7SSfryIoyDN1BmWfU51KSrp6M9yZDES_97486uKOxTfVCnvoJDyCGjJ4wV9c_b6dkJZSUtcsY3yA6jTZ1LKZrNL3mb7IbwSCktG8q3yHYhKl7UVOyQp1vUPVgTlpnrsomOxtmP9KtHi7EfBxNc7I3TI1iImIFts1ns0We_ERL9gtnsbVygze5WqA2G_Nq2z9rYRTax0WiwOrGTBMSwT350MAQ8-Dv3yMPF-f30Kr-ZXV5PJze5loLFXPAOW2SiLCotZUG1BFF1ElrJmoIW84YCawWvOWqgTakZx45jySs5r1tsgO-R03Xv6nm-xFan3x4GtfJmCX5UDoz6vrGmVwv3ogSVgrMmFRyvC7R3IXjsPm8ZVR_SVZKu_khXjCf86Ou_T_if5QRUa8DYzvklvDo_tCrCODjf-aTIBMX_W_0OYB2R9g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Jutooru, Indira ; Guthrie, Aaron S. ; Chadalapaka, Gayathri ; Pathi, Satya ; Kim, KyoungHyun ; Burghardt, Robert ; Jin, Un-Ho ; Safe, Stephen</creator><creatorcontrib>Jutooru, Indira ; Guthrie, Aaron S. ; Chadalapaka, Gayathri ; Pathi, Satya ; Kim, KyoungHyun ; Burghardt, Robert ; Jin, Un-Ho ; Safe, Stephen</creatorcontrib><description>Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced apoptosis and decreased pancreatic cancer cell growth and invasion, indicating that downregulation of Sp transcription factors is an important common mechanism of action for PEITC and other ROS-inducing anticancer agents.</description><identifier>ISSN: 1098-5549</identifier><identifier>ISSN: 0270-7306</identifier><identifier>EISSN: 1098-5549</identifier><identifier>DOI: 10.1128/MCB.01602-13</identifier><identifier>PMID: 24732804</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Anticarcinogenic Agents - pharmacology ; Apoptosis - genetics ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation - drug effects ; Enzyme Inhibitors - pharmacology ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Isothiocyanates - pharmacology ; Mice ; Mice, Nude ; MicroRNAs - biosynthesis ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - pathology ; Proto-Oncogene Proteins c-myc - genetics ; Reactive Oxygen Species - metabolism ; Repressor Proteins - biosynthesis ; Repressor Proteins - genetics ; RNA Interference ; RNA, Small Interfering ; Sp1 Transcription Factor - biosynthesis ; Sp1 Transcription Factor - genetics ; Sp3 Transcription Factor - biosynthesis ; Sp4 Transcription Factor - biosynthesis ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular and cellular biology, 2014-07, Vol.34 (13), p.2382-2395</ispartof><rights>Copyright © 2014, American Society for Microbiology 2014</rights><rights>Copyright © 2014, American Society for Microbiology. All Rights Reserved.</rights><rights>Copyright © 2014, American Society for Microbiology. All Rights Reserved. 2014 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-43fede14627c5520c5a47f5ad519202b90a1d4383eca096c13ef3e6375b8de9a3</citedby><cites>FETCH-LOGICAL-c541t-43fede14627c5520c5a47f5ad519202b90a1d4383eca096c13ef3e6375b8de9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054319/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054319/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24732804$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jutooru, Indira</creatorcontrib><creatorcontrib>Guthrie, Aaron S.</creatorcontrib><creatorcontrib>Chadalapaka, Gayathri</creatorcontrib><creatorcontrib>Pathi, Satya</creatorcontrib><creatorcontrib>Kim, KyoungHyun</creatorcontrib><creatorcontrib>Burghardt, Robert</creatorcontrib><creatorcontrib>Jin, Un-Ho</creatorcontrib><creatorcontrib>Safe, Stephen</creatorcontrib><title>Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents</title><title>Molecular and cellular biology</title><addtitle>Mol Cell Biol</addtitle><description>Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced apoptosis and decreased pancreatic cancer cell growth and invasion, indicating that downregulation of Sp transcription factors is an important common mechanism of action for PEITC and other ROS-inducing anticancer agents.</description><subject>Animals</subject><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Apoptosis - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Down-Regulation - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Isothiocyanates - pharmacology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>MicroRNAs - biosynthesis</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Repressor Proteins - biosynthesis</subject><subject>Repressor Proteins - genetics</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><subject>Sp1 Transcription Factor - biosynthesis</subject><subject>Sp1 Transcription Factor - genetics</subject><subject>Sp3 Transcription Factor - biosynthesis</subject><subject>Sp4 Transcription Factor - biosynthesis</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1098-5549</issn><issn>0270-7306</issn><issn>1098-5549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkFtLJDEQRoO4eH_zWfoH2G7SSfryIoyDN1BmWfU51KSrp6M9yZDES_97486uKOxTfVCnvoJDyCGjJ4wV9c_b6dkJZSUtcsY3yA6jTZ1LKZrNL3mb7IbwSCktG8q3yHYhKl7UVOyQp1vUPVgTlpnrsomOxtmP9KtHi7EfBxNc7I3TI1iImIFts1ns0We_ERL9gtnsbVygze5WqA2G_Nq2z9rYRTax0WiwOrGTBMSwT350MAQ8-Dv3yMPF-f30Kr-ZXV5PJze5loLFXPAOW2SiLCotZUG1BFF1ElrJmoIW84YCawWvOWqgTakZx45jySs5r1tsgO-R03Xv6nm-xFan3x4GtfJmCX5UDoz6vrGmVwv3ogSVgrMmFRyvC7R3IXjsPm8ZVR_SVZKu_khXjCf86Ou_T_if5QRUa8DYzvklvDo_tCrCODjf-aTIBMX_W_0OYB2R9g</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Jutooru, Indira</creator><creator>Guthrie, Aaron S.</creator><creator>Chadalapaka, Gayathri</creator><creator>Pathi, Satya</creator><creator>Kim, KyoungHyun</creator><creator>Burghardt, Robert</creator><creator>Jin, Un-Ho</creator><creator>Safe, Stephen</creator><general>Taylor & Francis</general><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20140701</creationdate><title>Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents</title><author>Jutooru, Indira ; Guthrie, Aaron S. ; Chadalapaka, Gayathri ; Pathi, Satya ; Kim, KyoungHyun ; Burghardt, Robert ; Jin, Un-Ho ; Safe, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-43fede14627c5520c5a47f5ad519202b90a1d4383eca096c13ef3e6375b8de9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Anticarcinogenic Agents - pharmacology</topic><topic>Apoptosis - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Down-Regulation - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Isothiocyanates - pharmacology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>MicroRNAs - biosynthesis</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Repressor Proteins - biosynthesis</topic><topic>Repressor Proteins - genetics</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering</topic><topic>Sp1 Transcription Factor - biosynthesis</topic><topic>Sp1 Transcription Factor - genetics</topic><topic>Sp3 Transcription Factor - biosynthesis</topic><topic>Sp4 Transcription Factor - biosynthesis</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jutooru, Indira</creatorcontrib><creatorcontrib>Guthrie, Aaron S.</creatorcontrib><creatorcontrib>Chadalapaka, Gayathri</creatorcontrib><creatorcontrib>Pathi, Satya</creatorcontrib><creatorcontrib>Kim, KyoungHyun</creatorcontrib><creatorcontrib>Burghardt, Robert</creatorcontrib><creatorcontrib>Jin, Un-Ho</creatorcontrib><creatorcontrib>Safe, Stephen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jutooru, Indira</au><au>Guthrie, Aaron S.</au><au>Chadalapaka, Gayathri</au><au>Pathi, Satya</au><au>Kim, KyoungHyun</au><au>Burghardt, Robert</au><au>Jin, Un-Ho</au><au>Safe, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>34</volume><issue>13</issue><spage>2382</spage><epage>2395</epage><pages>2382-2395</pages><issn>1098-5549</issn><issn>0270-7306</issn><eissn>1098-5549</eissn><abstract>Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced apoptosis and decreased pancreatic cancer cell growth and invasion, indicating that downregulation of Sp transcription factors is an important common mechanism of action for PEITC and other ROS-inducing anticancer agents.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>24732804</pmid><doi>10.1128/MCB.01602-13</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1098-5549 |
| ispartof | Molecular and cellular biology, 2014-07, Vol.34 (13), p.2382-2395 |
| issn | 1098-5549 0270-7306 1098-5549 |
| language | eng |
| recordid | cdi_pubmed_primary_24732804 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Anticarcinogenic Agents - pharmacology Apoptosis - genetics Cell Line, Tumor Cell Proliferation Down-Regulation - drug effects Enzyme Inhibitors - pharmacology Female Gene Expression Regulation, Neoplastic - drug effects Humans Isothiocyanates - pharmacology Mice Mice, Nude MicroRNAs - biosynthesis Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - pathology Proto-Oncogene Proteins c-myc - genetics Reactive Oxygen Species - metabolism Repressor Proteins - biosynthesis Repressor Proteins - genetics RNA Interference RNA, Small Interfering Sp1 Transcription Factor - biosynthesis Sp1 Transcription Factor - genetics Sp3 Transcription Factor - biosynthesis Sp4 Transcription Factor - biosynthesis Xenograft Model Antitumor Assays |
| title | Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T10%3A15%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mechanism%20of%20Action%20of%20Phenethylisothiocyanate%20and%20Other%20Reactive%20Oxygen%20Species-Inducing%20Anticancer%20Agents&rft.jtitle=Molecular%20and%20cellular%20biology&rft.au=Jutooru,%20Indira&rft.date=2014-07-01&rft.volume=34&rft.issue=13&rft.spage=2382&rft.epage=2395&rft.pages=2382-2395&rft.issn=1098-5549&rft.eissn=1098-5549&rft_id=info:doi/10.1128/MCB.01602-13&rft_dat=%3Cpubmed_cross%3E24732804%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/24732804&rfr_iscdi=true |