A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines...
Gespeichert in:
| Veröffentlicht in: | PloS one 2018-06, Vol.13 (6), p.e0199130-e0199130 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0199130 |
|---|---|
| container_issue | 6 |
| container_start_page | e0199130 |
| container_title | PloS one |
| container_volume | 13 |
| creator | Thakar, Manjusha Hu, Yue Morreale, Michael Lerner, Lane Ying Lin, Wan Sen, Rupashree Cai, Yi Karunasena, Enusha Thakar, Maya Saggi, Soren Keer, Harold Ahuja, Nita |
| description | Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action. |
| doi_str_mv | 10.1371/journal.pone.0199130 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2057888364</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A543865522</galeid><doaj_id>oai_doaj_org_article_c3ccffdba6304964815c74ae8b08da86</doaj_id><sourcerecordid>A543865522</sourcerecordid><originalsourceid>FETCH-LOGICAL-c653t-b68e9400418beca4bf089ecf40db19b043fb8572cf3ffa75783fb8a06c3e830f3</originalsourceid><addsrcrecordid>eNqNkl2L1DAUhoso7rr6D0QLgujFjEnTj-RGGBY_BhYW_LwMp-lJp0Mn6Sbp4vrrTXe6y4x44VXCyXPe5D15k-Q5JUvKKvpua0dnoF8O1uCSUCEoIw-SUypYtigzwh4e7E-SJ95vCSkYL8vHyUkmRFaJSpwmP1epsdfYpzh0LRoMnUp3thl7CJ1pU4i1kHo0vgvdb_TpAEY5hAlT2Pc-DTaFVG1wZ8MGHQw3-56nySMNvcdn83qWfP_44dv558XF5af1-epiocqChUVdchQ5ITnlNSrIa024QKVz0tRU1CRnuuZFlSnNtIaqqPhUAFIqhpwRzc6Sl3vdobdezjPxMiMR5ZyVeSTWe6KxsJWD63bgbqSFTt4WrGsluOinR6mYUlo3NZSM5KLMOS1UlQPymvAGeBm13s-3jfUOGxWNOuiPRI9PTLeRrb2WJaEsy0QUeDMLOHs1og9y1_lpkGDQjrfv5gWhFScRffUX-m93M9VCNNAZbeO9ahKVqyKP310UWRapt0eUsibgr9DC6L1cf_3y_-zlj2P29QG7QejDxtt-DJ01_hjM96By1nuH-n5mlMgpznfm5BRnOcc5tr04nPd9011-2R_TcfFI</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2057888364</pqid></control><display><type>article</type><title>A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent</title><source>PubMed (Medline)</source><source>PLoS</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Thakar, Manjusha ; Hu, Yue ; Morreale, Michael ; Lerner, Lane ; Ying Lin, Wan ; Sen, Rupashree ; Cai, Yi ; Karunasena, Enusha ; Thakar, Maya ; Saggi, Soren ; Keer, Harold ; Ahuja, Nita</creator><creatorcontrib>Thakar, Manjusha ; Hu, Yue ; Morreale, Michael ; Lerner, Lane ; Ying Lin, Wan ; Sen, Rupashree ; Cai, Yi ; Karunasena, Enusha ; Thakar, Maya ; Saggi, Soren ; Keer, Harold ; Ahuja, Nita</creatorcontrib><description>Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0199130</identifier><identifier>PMID: 29927979</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Antineoplastic Agents - pharmacology ; Apoptosis ; Azacitidine - analogs & derivatives ; Azacitidine - pharmacology ; Biology and Life Sciences ; Cancer therapies ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - pathology ; Care and treatment ; Caspase ; Cell adhesion & migration ; Cell Line, Tumor ; Cell lines ; Cell Survival - drug effects ; Chemotherapy ; Deoxyribonucleic acid ; DNA ; DNA (Cytosine-5-)-Methyltransferase 1 - metabolism ; DNA methylation ; DNA methyltransferase ; DNMT1 protein ; Drug resistance ; Epigenesis, Genetic - drug effects ; Epigenetic inheritance ; Epigenetics ; Gene expression ; Humans ; Immunotherapy ; Irinotecan ; Irinotecan - pharmacology ; Medical research ; Medicine and Health Sciences ; Metastasis ; Modulators ; Oncology ; Pancreas ; Pancreas - drug effects ; Pancreas - metabolism ; Pancreas - pathology ; Pancreatic cancer ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Patient outcomes ; Research and Analysis Methods ; Topoisomerase I Inhibitors - pharmacology ; Tumors</subject><ispartof>PloS one, 2018-06, Vol.13 (6), p.e0199130-e0199130</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Thakar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Thakar et al 2018 Thakar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-b68e9400418beca4bf089ecf40db19b043fb8572cf3ffa75783fb8a06c3e830f3</citedby><cites>FETCH-LOGICAL-c653t-b68e9400418beca4bf089ecf40db19b043fb8572cf3ffa75783fb8a06c3e830f3</cites><orcidid>0000-0002-3934-8640 ; 0000-0003-3610-9641</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013229/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013229/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29927979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thakar, Manjusha</creatorcontrib><creatorcontrib>Hu, Yue</creatorcontrib><creatorcontrib>Morreale, Michael</creatorcontrib><creatorcontrib>Lerner, Lane</creatorcontrib><creatorcontrib>Ying Lin, Wan</creatorcontrib><creatorcontrib>Sen, Rupashree</creatorcontrib><creatorcontrib>Cai, Yi</creatorcontrib><creatorcontrib>Karunasena, Enusha</creatorcontrib><creatorcontrib>Thakar, Maya</creatorcontrib><creatorcontrib>Saggi, Soren</creatorcontrib><creatorcontrib>Keer, Harold</creatorcontrib><creatorcontrib>Ahuja, Nita</creatorcontrib><title>A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.</description><subject>Adenocarcinoma</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Azacitidine - analogs & derivatives</subject><subject>Azacitidine - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Cancer therapies</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Care and treatment</subject><subject>Caspase</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1 - metabolism</subject><subject>DNA methylation</subject><subject>DNA methyltransferase</subject><subject>DNMT1 protein</subject><subject>Drug resistance</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Irinotecan</subject><subject>Irinotecan - pharmacology</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>Modulators</subject><subject>Oncology</subject><subject>Pancreas</subject><subject>Pancreas - drug effects</subject><subject>Pancreas - metabolism</subject><subject>Pancreas - pathology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Patient outcomes</subject><subject>Research and Analysis Methods</subject><subject>Topoisomerase I Inhibitors - pharmacology</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLgujFjEnTj-RGGBY_BhYW_LwMp-lJp0Mn6Sbp4vrrTXe6y4x44VXCyXPe5D15k-Q5JUvKKvpua0dnoF8O1uCSUCEoIw-SUypYtigzwh4e7E-SJ95vCSkYL8vHyUkmRFaJSpwmP1epsdfYpzh0LRoMnUp3thl7CJ1pU4i1kHo0vgvdb_TpAEY5hAlT2Pc-DTaFVG1wZ8MGHQw3-56nySMNvcdn83qWfP_44dv558XF5af1-epiocqChUVdchQ5ITnlNSrIa024QKVz0tRU1CRnuuZFlSnNtIaqqPhUAFIqhpwRzc6Sl3vdobdezjPxMiMR5ZyVeSTWe6KxsJWD63bgbqSFTt4WrGsluOinR6mYUlo3NZSM5KLMOS1UlQPymvAGeBm13s-3jfUOGxWNOuiPRI9PTLeRrb2WJaEsy0QUeDMLOHs1og9y1_lpkGDQjrfv5gWhFScRffUX-m93M9VCNNAZbeO9ahKVqyKP310UWRapt0eUsibgr9DC6L1cf_3y_-zlj2P29QG7QejDxtt-DJ01_hjM96By1nuH-n5mlMgpznfm5BRnOcc5tr04nPd9011-2R_TcfFI</recordid><startdate>20180621</startdate><enddate>20180621</enddate><creator>Thakar, Manjusha</creator><creator>Hu, Yue</creator><creator>Morreale, Michael</creator><creator>Lerner, Lane</creator><creator>Ying Lin, Wan</creator><creator>Sen, Rupashree</creator><creator>Cai, Yi</creator><creator>Karunasena, Enusha</creator><creator>Thakar, Maya</creator><creator>Saggi, Soren</creator><creator>Keer, Harold</creator><creator>Ahuja, Nita</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3934-8640</orcidid><orcidid>https://orcid.org/0000-0003-3610-9641</orcidid></search><sort><creationdate>20180621</creationdate><title>A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent</title><author>Thakar, Manjusha ; Hu, Yue ; Morreale, Michael ; Lerner, Lane ; Ying Lin, Wan ; Sen, Rupashree ; Cai, Yi ; Karunasena, Enusha ; Thakar, Maya ; Saggi, Soren ; Keer, Harold ; Ahuja, Nita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-b68e9400418beca4bf089ecf40db19b043fb8572cf3ffa75783fb8a06c3e830f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Azacitidine - analogs & derivatives</topic><topic>Azacitidine - pharmacology</topic><topic>Biology and Life Sciences</topic><topic>Cancer therapies</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Care and treatment</topic><topic>Caspase</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell Survival - drug effects</topic><topic>Chemotherapy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1 - metabolism</topic><topic>DNA methylation</topic><topic>DNA methyltransferase</topic><topic>DNMT1 protein</topic><topic>Drug resistance</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Irinotecan</topic><topic>Irinotecan - pharmacology</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Metastasis</topic><topic>Modulators</topic><topic>Oncology</topic><topic>Pancreas</topic><topic>Pancreas - drug effects</topic><topic>Pancreas - metabolism</topic><topic>Pancreas - pathology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Patient outcomes</topic><topic>Research and Analysis Methods</topic><topic>Topoisomerase I Inhibitors - pharmacology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thakar, Manjusha</creatorcontrib><creatorcontrib>Hu, Yue</creatorcontrib><creatorcontrib>Morreale, Michael</creatorcontrib><creatorcontrib>Lerner, Lane</creatorcontrib><creatorcontrib>Ying Lin, Wan</creatorcontrib><creatorcontrib>Sen, Rupashree</creatorcontrib><creatorcontrib>Cai, Yi</creatorcontrib><creatorcontrib>Karunasena, Enusha</creatorcontrib><creatorcontrib>Thakar, Maya</creatorcontrib><creatorcontrib>Saggi, Soren</creatorcontrib><creatorcontrib>Keer, Harold</creatorcontrib><creatorcontrib>Ahuja, Nita</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - current)</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thakar, Manjusha</au><au>Hu, Yue</au><au>Morreale, Michael</au><au>Lerner, Lane</au><au>Ying Lin, Wan</au><au>Sen, Rupashree</au><au>Cai, Yi</au><au>Karunasena, Enusha</au><au>Thakar, Maya</au><au>Saggi, Soren</au><au>Keer, Harold</au><au>Ahuja, Nita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-06-21</date><risdate>2018</risdate><volume>13</volume><issue>6</issue><spage>e0199130</spage><epage>e0199130</epage><pages>e0199130-e0199130</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29927979</pmid><doi>10.1371/journal.pone.0199130</doi><tpages>e0199130</tpages><orcidid>https://orcid.org/0000-0002-3934-8640</orcidid><orcidid>https://orcid.org/0000-0003-3610-9641</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-06, Vol.13 (6), p.e0199130-e0199130 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2057888364 |
| source | PubMed (Medline); PLoS; MEDLINE; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Adenocarcinoma Antineoplastic Agents - pharmacology Apoptosis Azacitidine - analogs & derivatives Azacitidine - pharmacology Biology and Life Sciences Cancer therapies Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Care and treatment Caspase Cell adhesion & migration Cell Line, Tumor Cell lines Cell Survival - drug effects Chemotherapy Deoxyribonucleic acid DNA DNA (Cytosine-5-)-Methyltransferase 1 - metabolism DNA methylation DNA methyltransferase DNMT1 protein Drug resistance Epigenesis, Genetic - drug effects Epigenetic inheritance Epigenetics Gene expression Humans Immunotherapy Irinotecan Irinotecan - pharmacology Medical research Medicine and Health Sciences Metastasis Modulators Oncology Pancreas Pancreas - drug effects Pancreas - metabolism Pancreas - pathology Pancreatic cancer Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Patient outcomes Research and Analysis Methods Topoisomerase I Inhibitors - pharmacology Tumors |
| title | A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T19%3A04%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20epigenetic%20modulating%20agent%20sensitizes%20pancreatic%20cells%20to%20a%20chemotherapy%20agent&rft.jtitle=PloS%20one&rft.au=Thakar,%20Manjusha&rft.date=2018-06-21&rft.volume=13&rft.issue=6&rft.spage=e0199130&rft.epage=e0199130&rft.pages=e0199130-e0199130&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0199130&rft_dat=%3Cgale_plos_%3EA543865522%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2057888364&rft_id=info:pmid/29927979&rft_galeid=A543865522&rft_doaj_id=oai_doaj_org_article_c3ccffdba6304964815c74ae8b08da86&rfr_iscdi=true |