Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB
Abstract Targeting of signal transduction pathways and transcriptional regulation represents an attractive approach for less toxic anti-leukaemic therapy. We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, r...
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| Veröffentlicht in: | Leukemia research 2010-01, Vol.34 (1), p.77-84 |
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| container_title | Leukemia research |
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| creator | Erikstein, Bjarte Skoe McCormack, Emmet Tronstad, Karl Johan Schwede, Frank Berge, Rolf Gjertsen, Bjørn Tore |
| description | Abstract Targeting of signal transduction pathways and transcriptional regulation represents an attractive approach for less toxic anti-leukaemic therapy. We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, resulting in synergistic decrease in viability of AML cell lines. PKA isoform II activation appeared to be involved in inhibition of proliferation but not induction of apoptosis in HL-60 cells. Inhibition of CREB function protected against this anti-leukaemic effect with higher efficiency than enforced Bcl-2 expression. Preclinical studies employing the rat AML model Brown Norwegian Myeloid Leukaemia also indicated anti-leukaemic activity of the combination therapy in vivo . In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential. |
| doi_str_mv | 10.1016/j.leukres.2009.09.005 |
| format | Article |
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We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, resulting in synergistic decrease in viability of AML cell lines. PKA isoform II activation appeared to be involved in inhibition of proliferation but not induction of apoptosis in HL-60 cells. Inhibition of CREB function protected against this anti-leukaemic effect with higher efficiency than enforced Bcl-2 expression. Preclinical studies employing the rat AML model Brown Norwegian Myeloid Leukaemia also indicated anti-leukaemic activity of the combination therapy in vivo . In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential.</description><identifier>ISSN: 0145-2126</identifier><identifier>EISSN: 1873-5835</identifier><identifier>DOI: 10.1016/j.leukres.2009.09.005</identifier><identifier>PMID: 19786302</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acute myelogenous leukaemia ; Animals ; Bcl-2 ; cAMP response element binding ; Chromatography, High Pressure Liquid ; Cyclic AMP ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Drug Synergism ; Enzyme Activators - pharmacology ; Enzyme Activators - therapeutic use ; Hematology, Oncology and Palliative Medicine ; HL-60 Cells ; Humans ; Inducible cAMP early repressor ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - metabolism ; Peroxisome proliferator-activated receptor ; Peroxisome Proliferator-Activated Receptors - agonists ; Protein kinase A ; Rats ; Sulfides - pharmacology ; Sulfides - therapeutic use ; Tetradecylthioacetic acid</subject><ispartof>Leukemia research, 2010-01, Vol.34 (1), p.77-84</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><rights>2009 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-400fd5f7bd4b434cd5ed96275475444954cf1efecc4b0fec2c2dda2a2de6e4fd3</citedby><cites>FETCH-LOGICAL-c450t-400fd5f7bd4b434cd5ed96275475444954cf1efecc4b0fec2c2dda2a2de6e4fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.leukres.2009.09.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19786302$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Erikstein, Bjarte Skoe</creatorcontrib><creatorcontrib>McCormack, Emmet</creatorcontrib><creatorcontrib>Tronstad, Karl Johan</creatorcontrib><creatorcontrib>Schwede, Frank</creatorcontrib><creatorcontrib>Berge, Rolf</creatorcontrib><creatorcontrib>Gjertsen, Bjørn Tore</creatorcontrib><title>Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB</title><title>Leukemia research</title><addtitle>Leuk Res</addtitle><description>Abstract Targeting of signal transduction pathways and transcriptional regulation represents an attractive approach for less toxic anti-leukaemic therapy. We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, resulting in synergistic decrease in viability of AML cell lines. PKA isoform II activation appeared to be involved in inhibition of proliferation but not induction of apoptosis in HL-60 cells. Inhibition of CREB function protected against this anti-leukaemic effect with higher efficiency than enforced Bcl-2 expression. Preclinical studies employing the rat AML model Brown Norwegian Myeloid Leukaemia also indicated anti-leukaemic activity of the combination therapy in vivo . In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential.</description><subject>Acute myelogenous leukaemia</subject><subject>Animals</subject><subject>Bcl-2</subject><subject>cAMP response element binding</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Drug Synergism</subject><subject>Enzyme Activators - pharmacology</subject><subject>Enzyme Activators - therapeutic use</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Inducible cAMP early repressor</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Peroxisome proliferator-activated receptor</subject><subject>Peroxisome Proliferator-Activated Receptors - agonists</subject><subject>Protein kinase A</subject><subject>Rats</subject><subject>Sulfides - pharmacology</subject><subject>Sulfides - therapeutic use</subject><subject>Tetradecylthioacetic acid</subject><issn>0145-2126</issn><issn>1873-5835</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUl2LEzEUDaK4dfUnKHnybepNJpl2XpRa1g-oWFZ9Dmlyp007TbpJZqH_wR9thhYEX4QDl4Rz70nOuYS8ZjBlwJp3-2mPwyFimnKAdjoC5BMyYfNZXcl5LZ-SCTAhK854c0NepLSHwmhZ-5zcsHY2b2rgE_J7HUNG5-nBeZ2QLqg22T3qHGKi2luad0hP2lfr9eKe6m3wLmWaMUdt0Zz7vHNBG8zOlEZnKfbOuEzT2WPcFup477OrxsdqPJYjdh2anGjRXHxblfkxDNsdXd7ffXxJnnW6T_jqWm_Jr093P5dfqtX3z1-Xi1VlhIRcCYDOym62sWIjamGsRNs2fCZFgRCtFKZjWFSM2EAp3HBrNdfcYoOis_UteXuZe4rhYcCU1dElg32vPYYhqWJZPaIQ5YVoYkgpYqdO0R11PCsGaoxB7dU1BjXGoEaALH1vrgLD5oj2b9fV90L4cCFg-eajw6iScegNWheLO8oG91-J9_9MML3zzuj-gGdM-zBEXzxUTCWuQP0Yd2FcBWgBRCN5_QdOg7O8</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Erikstein, Bjarte Skoe</creator><creator>McCormack, Emmet</creator><creator>Tronstad, Karl Johan</creator><creator>Schwede, Frank</creator><creator>Berge, Rolf</creator><creator>Gjertsen, Bjørn Tore</creator><general>Elsevier Ltd</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20100101</creationdate><title>Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB</title><author>Erikstein, Bjarte Skoe ; McCormack, Emmet ; Tronstad, Karl Johan ; Schwede, Frank ; Berge, Rolf ; Gjertsen, Bjørn Tore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-400fd5f7bd4b434cd5ed96275475444954cf1efecc4b0fec2c2dda2a2de6e4fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acute myelogenous leukaemia</topic><topic>Animals</topic><topic>Bcl-2</topic><topic>cAMP response element binding</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Drug Synergism</topic><topic>Enzyme Activators - pharmacology</topic><topic>Enzyme Activators - therapeutic use</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Inducible cAMP early repressor</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Peroxisome proliferator-activated receptor</topic><topic>Peroxisome Proliferator-Activated Receptors - agonists</topic><topic>Protein kinase A</topic><topic>Rats</topic><topic>Sulfides - pharmacology</topic><topic>Sulfides - therapeutic use</topic><topic>Tetradecylthioacetic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erikstein, Bjarte Skoe</creatorcontrib><creatorcontrib>McCormack, Emmet</creatorcontrib><creatorcontrib>Tronstad, Karl Johan</creatorcontrib><creatorcontrib>Schwede, Frank</creatorcontrib><creatorcontrib>Berge, Rolf</creatorcontrib><creatorcontrib>Gjertsen, Bjørn Tore</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Leukemia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erikstein, Bjarte Skoe</au><au>McCormack, Emmet</au><au>Tronstad, Karl Johan</au><au>Schwede, Frank</au><au>Berge, Rolf</au><au>Gjertsen, Bjørn Tore</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB</atitle><jtitle>Leukemia research</jtitle><addtitle>Leuk Res</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>34</volume><issue>1</issue><spage>77</spage><epage>84</epage><pages>77-84</pages><issn>0145-2126</issn><eissn>1873-5835</eissn><abstract>Abstract Targeting of signal transduction pathways and transcriptional regulation represents an attractive approach for less toxic anti-leukaemic therapy. We combined protein kinase A (PKA) activation with a pan-peroxisome proliferator-activated receptor (PPAR) activator tetradecylthioacetic acid, resulting in synergistic decrease in viability of AML cell lines. PKA isoform II activation appeared to be involved in inhibition of proliferation but not induction of apoptosis in HL-60 cells. Inhibition of CREB function protected against this anti-leukaemic effect with higher efficiency than enforced Bcl-2 expression. Preclinical studies employing the rat AML model Brown Norwegian Myeloid Leukaemia also indicated anti-leukaemic activity of the combination therapy in vivo . In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19786302</pmid><doi>10.1016/j.leukres.2009.09.005</doi><tpages>8</tpages></addata></record> |
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| subjects | Acute myelogenous leukaemia Animals Bcl-2 cAMP response element binding Chromatography, High Pressure Liquid Cyclic AMP Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Drug Synergism Enzyme Activators - pharmacology Enzyme Activators - therapeutic use Hematology, Oncology and Palliative Medicine HL-60 Cells Humans Inducible cAMP early repressor Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - metabolism Peroxisome proliferator-activated receptor Peroxisome Proliferator-Activated Receptors - agonists Protein kinase A Rats Sulfides - pharmacology Sulfides - therapeutic use Tetradecylthioacetic acid |
| title | Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB |
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