The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM
We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo . In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the c...
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| Veröffentlicht in: | Scientific reports 2015-08, Vol.5 (1), p.13001-13001, Article 13001 |
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| creator | Follin-Arbelet, Virginie Misund, Kristine Hallan Naderi, Elin Ugland, Hege Sundan, Anders Kiil Blomhoff, Heidi |
| description | We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both
in vitro
and
in vivo
. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM. |
| doi_str_mv | 10.1038/srep13001 |
| format | Article |
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in vitro
and
in vivo
. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep13001</identifier><identifier>PMID: 26306624</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1059 ; 631/80/82/23 ; 631/80/86 ; 692/699/67/1990/804 ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - metabolism ; Bcl protein ; Bcl-2 protein ; Bcl-2-Like Protein 11 ; BIM protein ; Bortezomib ; Cell death ; Cell Line, Tumor ; Colforsin - administration & dosage ; Cyclic AMP ; Cyclophosphamide ; Dexamethasone ; Dexamethasone - administration & dosage ; Dose-Response Relationship, Drug ; Doxorubicin ; Drug Synergism ; Forskolin ; Humanities and Social Sciences ; Humans ; Melphalan ; Membrane Proteins - metabolism ; multidisciplinary ; Multiple myeloma ; Multiple Myeloma - drug therapy ; Multiple Myeloma - metabolism ; Multiple Myeloma - pathology ; Proto-Oncogene Proteins - metabolism ; Science ; Side effects ; Steroids ; Synergistic effect ; Treatment Outcome</subject><ispartof>Scientific reports, 2015-08, Vol.5 (1), p.13001-13001, Article 13001</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Aug 2015</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-3a667906424382edc44259dba883400c5016d95f813a2977b4c9038344cf6313</citedby><cites>FETCH-LOGICAL-c462t-3a667906424382edc44259dba883400c5016d95f813a2977b4c9038344cf6313</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/PMC4549684/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549684/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,26567,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26306624$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Follin-Arbelet, Virginie</creatorcontrib><creatorcontrib>Misund, Kristine</creatorcontrib><creatorcontrib>Hallan Naderi, Elin</creatorcontrib><creatorcontrib>Ugland, Hege</creatorcontrib><creatorcontrib>Sundan, Anders</creatorcontrib><creatorcontrib>Kiil Blomhoff, Heidi</creatorcontrib><title>The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both
in vitro
and
in vivo
. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.</description><subject>631/67/1059</subject><subject>631/80/82/23</subject><subject>631/80/86</subject><subject>692/699/67/1990/804</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Bcl protein</subject><subject>Bcl-2 protein</subject><subject>Bcl-2-Like Protein 11</subject><subject>BIM protein</subject><subject>Bortezomib</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Colforsin - administration & dosage</subject><subject>Cyclic AMP</subject><subject>Cyclophosphamide</subject><subject>Dexamethasone</subject><subject>Dexamethasone - administration & dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Doxorubicin</subject><subject>Drug Synergism</subject><subject>Forskolin</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Melphalan</subject><subject>Membrane Proteins - metabolism</subject><subject>multidisciplinary</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - metabolism</subject><subject>Multiple Myeloma - pathology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Science</subject><subject>Side effects</subject><subject>Steroids</subject><subject>Synergistic effect</subject><subject>Treatment Outcome</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>3HK</sourceid><recordid>eNplkV9PHCEUxYmpqUZ96BewJH1pm6zlz4UZXpq0plUTTV_2nbAMs8t2BlaYsd1--qKrm1V5gXB_9x4OB6F3lJxRwusvObkV5YTQPXTICIgJ44y92TkfoJOcl6QswRRQ9RYdMMmJlAwO0XK6cDiYYUymwzb2qziGBrcx5d-x8wHndXBp7v-5jP_4YYEb99f0bliYHIPDQ8Q-NKN12LquK0VTkNLVr10Xe_Nwm_GdN_j71c0x2m9Nl93J436Epj9_TM8vJ9e_Lq7Ov11PLEg2TLiRslJEAgNeM9dYACZUMzN1zYEQKwiVjRJtTblhqqpmYFX5Bw5gW8kpP0JfN2NX46wv7S4MxZteJd-btNbReP28EvxCz-OdBgFK1lAGvN8MsMnnwQcdYjKaklowLRl7kPj4KJHi7ejyoHuf772a4OKYNa1IJQQIoQr64QW6jGMKxb-mtVIVVIKLQn16koy5BNpun0uJvk9Zb1Mu7Omuvy35lGkBPm-AXEph7tKO5Ktp_wH7_K8u</recordid><startdate>20150826</startdate><enddate>20150826</enddate><creator>Follin-Arbelet, Virginie</creator><creator>Misund, Kristine</creator><creator>Hallan Naderi, Elin</creator><creator>Ugland, Hege</creator><creator>Sundan, Anders</creator><creator>Kiil Blomhoff, Heidi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>3HK</scope><scope>5PM</scope></search><sort><creationdate>20150826</creationdate><title>The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM</title><author>Follin-Arbelet, Virginie ; Misund, Kristine ; Hallan Naderi, Elin ; Ugland, Hege ; Sundan, Anders ; Kiil Blomhoff, Heidi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-3a667906424382edc44259dba883400c5016d95f813a2977b4c9038344cf6313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/67/1059</topic><topic>631/80/82/23</topic><topic>631/80/86</topic><topic>692/699/67/1990/804</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Bcl protein</topic><topic>Bcl-2 protein</topic><topic>Bcl-2-Like Protein 11</topic><topic>BIM protein</topic><topic>Bortezomib</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Colforsin - administration & dosage</topic><topic>Cyclic AMP</topic><topic>Cyclophosphamide</topic><topic>Dexamethasone</topic><topic>Dexamethasone - administration & dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Doxorubicin</topic><topic>Drug Synergism</topic><topic>Forskolin</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Melphalan</topic><topic>Membrane Proteins - metabolism</topic><topic>multidisciplinary</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - metabolism</topic><topic>Multiple Myeloma - pathology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Science</topic><topic>Side effects</topic><topic>Steroids</topic><topic>Synergistic effect</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Follin-Arbelet, Virginie</creatorcontrib><creatorcontrib>Misund, Kristine</creatorcontrib><creatorcontrib>Hallan Naderi, Elin</creatorcontrib><creatorcontrib>Ugland, Hege</creatorcontrib><creatorcontrib>Sundan, Anders</creatorcontrib><creatorcontrib>Kiil Blomhoff, Heidi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Follin-Arbelet, Virginie</au><au>Misund, Kristine</au><au>Hallan Naderi, Elin</au><au>Ugland, Hege</au><au>Sundan, Anders</au><au>Kiil Blomhoff, Heidi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-08-26</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>13001</spage><epage>13001</epage><pages>13001-13001</pages><artnum>13001</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both
in vitro
and
in vivo
. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26306624</pmid><doi>10.1038/srep13001</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; NORA - Norwegian Open Research Archives; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/67/1059 631/80/82/23 631/80/86 692/699/67/1990/804 Antineoplastic Combined Chemotherapy Protocols - administration & dosage Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - metabolism Bcl protein Bcl-2 protein Bcl-2-Like Protein 11 BIM protein Bortezomib Cell death Cell Line, Tumor Colforsin - administration & dosage Cyclic AMP Cyclophosphamide Dexamethasone Dexamethasone - administration & dosage Dose-Response Relationship, Drug Doxorubicin Drug Synergism Forskolin Humanities and Social Sciences Humans Melphalan Membrane Proteins - metabolism multidisciplinary Multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - metabolism Multiple Myeloma - pathology Proto-Oncogene Proteins - metabolism Science Side effects Steroids Synergistic effect Treatment Outcome |
| title | The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM |
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