Investigation of intracellular signalling events mediating the mechanism of action of 7-hydroxycoumarin and 6-nitro-7-hdroxycoumarin in human renal cells
Previously, 7-hydroxycoumarin (7-OHC) and 6-nitro-7-hydroxycoumarin (6-NO 2-7-OHC) have been shown to be potent and selective anti-proliferative agents to the human renal cell carcinoma (RCC) cell line, A-498. Their effect on mitogen-activated protein kinases (MAPK's) was investigated. 6-NO 2-7...
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| Veröffentlicht in: | Cancer letters 2004-03, Vol.205 (1), p.69-79 |
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| creator | Finn, Gregory J Creaven, Bernadette S Egan, Denise A |
| description | Previously, 7-hydroxycoumarin (7-OHC) and 6-nitro-7-hydroxycoumarin (6-NO
2-7-OHC) have been shown to be potent and selective anti-proliferative agents to the human renal cell carcinoma (RCC) cell line, A-498. Their effect on mitogen-activated protein kinases (MAPK's) was investigated. 6-NO
2-7-OHC was shown to alter the phosphorylation status of ERK1/ERK2, p38 and SAPK, while 7-OHC activated ERK1/ERK2 but had no effect on p38 and SAPK. Also, 7-OHC inhibited topoisomerase II mediated relaxation of DNA, while neither compound was a substrate for P-glycoprotein (P-gp) mediated multi-drug resistance (MDR). Therefore, 6-NO
2-7-OHC, rather than 7-OHC, modulated signalling events associated with cellular differentiation and apoptosis, suggesting its mechanism of action may be the promotion of cellular maturation and/or death. Consequently, 6-NO
2-7-OHC may represent a novel therapeutic agent for the treatment of RCC's. |
| doi_str_mv | 10.1016/j.canlet.2003.09.024 |
| format | Article |
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2-7-OHC) have been shown to be potent and selective anti-proliferative agents to the human renal cell carcinoma (RCC) cell line, A-498. Their effect on mitogen-activated protein kinases (MAPK's) was investigated. 6-NO
2-7-OHC was shown to alter the phosphorylation status of ERK1/ERK2, p38 and SAPK, while 7-OHC activated ERK1/ERK2 but had no effect on p38 and SAPK. Also, 7-OHC inhibited topoisomerase II mediated relaxation of DNA, while neither compound was a substrate for P-glycoprotein (P-gp) mediated multi-drug resistance (MDR). Therefore, 6-NO
2-7-OHC, rather than 7-OHC, modulated signalling events associated with cellular differentiation and apoptosis, suggesting its mechanism of action may be the promotion of cellular maturation and/or death. Consequently, 6-NO
2-7-OHC may represent a novel therapeutic agent for the treatment of RCC's.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2003.09.024</identifier><identifier>PMID: 15036663</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>6-Nitro-7-hydroxycoumarin ; Antineoplastic Agents - pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Carcinoma, Renal Cell - drug therapy ; Carcinoma, Renal Cell - metabolism ; Cell cycle ; Cell Line, Tumor ; Coumarins - pharmacology ; DNA Topoisomerases, Type II - drug effects ; Drug Resistance, Multiple ; Humans ; Immunoblotting ; In vitro ; Kinases ; Medical research ; Mitogen-activated protein kinase ; Mitogen-Activated Protein Kinases - drug effects ; Phosphorylation - drug effects ; Renal cell carcinoma ; Signal Transduction - drug effects ; Studies ; Umbelliferones - pharmacology</subject><ispartof>Cancer letters, 2004-03, Vol.205 (1), p.69-79</ispartof><rights>2003 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Mar 8, 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-f9bb70304e492e65c067720aa0b442e395ced6c7c953c6cebec3eaa1ef8647f3</citedby><cites>FETCH-LOGICAL-c386t-f9bb70304e492e65c067720aa0b442e395ced6c7c953c6cebec3eaa1ef8647f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2003.09.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15036663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Finn, Gregory J</creatorcontrib><creatorcontrib>Creaven, Bernadette S</creatorcontrib><creatorcontrib>Egan, Denise A</creatorcontrib><title>Investigation of intracellular signalling events mediating the mechanism of action of 7-hydroxycoumarin and 6-nitro-7-hdroxycoumarin in human renal cells</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Previously, 7-hydroxycoumarin (7-OHC) and 6-nitro-7-hydroxycoumarin (6-NO
2-7-OHC) have been shown to be potent and selective anti-proliferative agents to the human renal cell carcinoma (RCC) cell line, A-498. Their effect on mitogen-activated protein kinases (MAPK's) was investigated. 6-NO
2-7-OHC was shown to alter the phosphorylation status of ERK1/ERK2, p38 and SAPK, while 7-OHC activated ERK1/ERK2 but had no effect on p38 and SAPK. Also, 7-OHC inhibited topoisomerase II mediated relaxation of DNA, while neither compound was a substrate for P-glycoprotein (P-gp) mediated multi-drug resistance (MDR). Therefore, 6-NO
2-7-OHC, rather than 7-OHC, modulated signalling events associated with cellular differentiation and apoptosis, suggesting its mechanism of action may be the promotion of cellular maturation and/or death. Consequently, 6-NO
2-7-OHC may represent a novel therapeutic agent for the treatment of RCC's.</description><subject>6-Nitro-7-hydroxycoumarin</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Carcinoma, Renal Cell - drug therapy</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Coumarins - pharmacology</subject><subject>DNA Topoisomerases, Type II - drug effects</subject><subject>Drug Resistance, Multiple</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>In vitro</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Mitogen-activated protein kinase</subject><subject>Mitogen-Activated Protein Kinases - drug effects</subject><subject>Phosphorylation - drug effects</subject><subject>Renal cell carcinoma</subject><subject>Signal Transduction - drug effects</subject><subject>Studies</subject><subject>Umbelliferones - pharmacology</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UVGL1DAQDqJ4e6f_QCQg-NY6bdqkfRHkUO_gwJd7D2k63c3STc4kXdyf4r91yq6IPgiBZDLffDPzfYy9qaCsoJIf9qU1fsZc1gCihL6EunnGNlWn6kL1HTxnGxDQFKIT7RW7TmkPAG2j2pfsqmpBSCnFhv2890dM2W1NdsHzMHHnczQW53mZTeTJbb2ZZ-e3HI_oc-IHHB2B6SPvkCK7M96lw1pq7G8SVexOYww_TjYsBxOd58aPXBbe5RgKyv6dpLOjp-cRqRtfu6dX7MVk5oSvL_cNe_zy-fH2rnj49vX-9tNDYUUnczH1w6DWRbHpa5StBalUDcbA0DQ1ir61OEqrbN8KKy0OaAUaU-HUyUZN4oa9P9M-xfB9ISn0waV1AOMxLEmrSjVE0hHw3T_AfVgijZs0ydmSniBaQjVnlI0hpYiTfoqOljzpCvTqm97rs2969U1Dr8k3Knt7IV8GEvhP0cUoAnw8A5CkODqMOlmHnnZzEW3WY3D_7_AL7RiuqQ</recordid><startdate>20040308</startdate><enddate>20040308</enddate><creator>Finn, Gregory J</creator><creator>Creaven, Bernadette S</creator><creator>Egan, Denise A</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20040308</creationdate><title>Investigation of intracellular signalling events mediating the mechanism of action of 7-hydroxycoumarin and 6-nitro-7-hdroxycoumarin in human renal cells</title><author>Finn, Gregory J ; Creaven, Bernadette S ; Egan, Denise A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-f9bb70304e492e65c067720aa0b442e395ced6c7c953c6cebec3eaa1ef8647f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>6-Nitro-7-hydroxycoumarin</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Carcinoma, Renal Cell - drug therapy</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Coumarins - pharmacology</topic><topic>DNA Topoisomerases, Type II - drug effects</topic><topic>Drug Resistance, Multiple</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>In vitro</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinases - drug effects</topic><topic>Phosphorylation - drug effects</topic><topic>Renal cell carcinoma</topic><topic>Signal Transduction - drug effects</topic><topic>Studies</topic><topic>Umbelliferones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Finn, Gregory J</creatorcontrib><creatorcontrib>Creaven, Bernadette S</creatorcontrib><creatorcontrib>Egan, Denise A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Finn, Gregory J</au><au>Creaven, Bernadette S</au><au>Egan, Denise A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of intracellular signalling events mediating the mechanism of action of 7-hydroxycoumarin and 6-nitro-7-hdroxycoumarin in human renal cells</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2004-03-08</date><risdate>2004</risdate><volume>205</volume><issue>1</issue><spage>69</spage><epage>79</epage><pages>69-79</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Previously, 7-hydroxycoumarin (7-OHC) and 6-nitro-7-hydroxycoumarin (6-NO
2-7-OHC) have been shown to be potent and selective anti-proliferative agents to the human renal cell carcinoma (RCC) cell line, A-498. Their effect on mitogen-activated protein kinases (MAPK's) was investigated. 6-NO
2-7-OHC was shown to alter the phosphorylation status of ERK1/ERK2, p38 and SAPK, while 7-OHC activated ERK1/ERK2 but had no effect on p38 and SAPK. Also, 7-OHC inhibited topoisomerase II mediated relaxation of DNA, while neither compound was a substrate for P-glycoprotein (P-gp) mediated multi-drug resistance (MDR). Therefore, 6-NO
2-7-OHC, rather than 7-OHC, modulated signalling events associated with cellular differentiation and apoptosis, suggesting its mechanism of action may be the promotion of cellular maturation and/or death. Consequently, 6-NO
2-7-OHC may represent a novel therapeutic agent for the treatment of RCC's.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>15036663</pmid><doi>10.1016/j.canlet.2003.09.024</doi><tpages>11</tpages></addata></record> |
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| ispartof | Cancer letters, 2004-03, Vol.205 (1), p.69-79 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 6-Nitro-7-hydroxycoumarin Antineoplastic Agents - pharmacology ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Carcinoma, Renal Cell - drug therapy Carcinoma, Renal Cell - metabolism Cell cycle Cell Line, Tumor Coumarins - pharmacology DNA Topoisomerases, Type II - drug effects Drug Resistance, Multiple Humans Immunoblotting In vitro Kinases Medical research Mitogen-activated protein kinase Mitogen-Activated Protein Kinases - drug effects Phosphorylation - drug effects Renal cell carcinoma Signal Transduction - drug effects Studies Umbelliferones - pharmacology |
| title | Investigation of intracellular signalling events mediating the mechanism of action of 7-hydroxycoumarin and 6-nitro-7-hdroxycoumarin in human renal cells |
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