Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death
Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Δ-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viabi...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2007-12, Vol.364 (1), p.131-137 |
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| creator | Athanasiou, Andriani Clarke, Anna B. Turner, Amy E. Kumaran, Nethia M. Vakilpour, Sara Smith, Paul A. Bagiokou, Dimitra Bradshaw, Tracey D. Westwell, Andrew D. Fang, Lin Lobo, Dileep N. Constantinescu, Cris S. Calabrese, Vittorio Loesch, Andrzej Alexander, Stephen P.H. Clothier, Richard H. Kendall, David A. Bates, Timothy E. |
| description | Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Δ-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viability showed that AEA and THC caused significant increases in OD 595
nm at lower concentrations (10–50
μM) and significant decreases at 100
μM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II–III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors. |
| doi_str_mv | 10.1016/j.bbrc.2007.09.107 |
| format | Article |
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nm at lower concentrations (10–50
μM) and significant decreases at 100
μM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II–III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2007.09.107</identifier><identifier>PMID: 17931597</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anandamide ; Apoptosis ; Apoptosis - drug effects ; Arachidonic Acids - pharmacology ; Cannabinoid ; Cannabinoid Receptor Agonists ; Cannabinoids - pharmacology ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Dronabinol - analogs & derivatives ; Dronabinol - pharmacology ; Electron Transport Complex I - drug effects ; Electron Transport Complex II - drug effects ; Electron Transport Complex III - drug effects ; Endocannabinoids ; HU 210 ; Humans ; Hydrogen Peroxide - metabolism ; Janus ; Lung Neoplasms ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - physiology ; Models, Biological ; Oxygen Consumption - drug effects ; Polyunsaturated Alkamides - pharmacology ; Δ-9-Tetrahydrocannabinol</subject><ispartof>Biochemical and biophysical research communications, 2007-12, Vol.364 (1), p.131-137</ispartof><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-d11c0c1f04b01792774b496fdd64c8841df674594f20869302455e38bb29cd73</citedby><cites>FETCH-LOGICAL-c451t-d11c0c1f04b01792774b496fdd64c8841df674594f20869302455e38bb29cd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X07021079$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17931597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Athanasiou, Andriani</creatorcontrib><creatorcontrib>Clarke, Anna B.</creatorcontrib><creatorcontrib>Turner, Amy E.</creatorcontrib><creatorcontrib>Kumaran, Nethia M.</creatorcontrib><creatorcontrib>Vakilpour, Sara</creatorcontrib><creatorcontrib>Smith, Paul A.</creatorcontrib><creatorcontrib>Bagiokou, Dimitra</creatorcontrib><creatorcontrib>Bradshaw, Tracey D.</creatorcontrib><creatorcontrib>Westwell, Andrew D.</creatorcontrib><creatorcontrib>Fang, Lin</creatorcontrib><creatorcontrib>Lobo, Dileep N.</creatorcontrib><creatorcontrib>Constantinescu, Cris S.</creatorcontrib><creatorcontrib>Calabrese, Vittorio</creatorcontrib><creatorcontrib>Loesch, Andrzej</creatorcontrib><creatorcontrib>Alexander, Stephen P.H.</creatorcontrib><creatorcontrib>Clothier, Richard H.</creatorcontrib><creatorcontrib>Kendall, David A.</creatorcontrib><creatorcontrib>Bates, Timothy E.</creatorcontrib><title>Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Δ-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viability showed that AEA and THC caused significant increases in OD 595
nm at lower concentrations (10–50
μM) and significant decreases at 100
μM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II–III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.</description><subject>Anandamide</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Cannabinoid</subject><subject>Cannabinoid Receptor Agonists</subject><subject>Cannabinoids - pharmacology</subject><subject>Carcinoma, Non-Small-Cell Lung</subject><subject>Cell Line, Tumor</subject><subject>Dronabinol - analogs & derivatives</subject><subject>Dronabinol - pharmacology</subject><subject>Electron Transport Complex I - drug effects</subject><subject>Electron Transport Complex II - drug effects</subject><subject>Electron Transport Complex III - drug effects</subject><subject>Endocannabinoids</subject><subject>HU 210</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Janus</subject><subject>Lung Neoplasms</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - physiology</subject><subject>Models, Biological</subject><subject>Oxygen Consumption - drug effects</subject><subject>Polyunsaturated Alkamides - pharmacology</subject><subject>Δ-9-Tetrahydrocannabinol</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuKFDEUhoMoTjv6Ai4kK3fVnqRSlYq4GRpvMOBmFu5CbmWlqUraJOUwr-LTmqIbBlzo6sDPn49z8iH0msCeAOnfHfdaJ7OnAHwPomb8CdoRENBQAuwp2gFA31BBvl-hFzkfAQhhvXiOrggXLekE36HfBxWC0j5Eb3Fyxp1KTFj9iMHnkrFKDi--RDPFYJNXM_Zh8romKb_HN3gNfvTO4unhFMvkss84jniK99g8cjNeol1nVf5mjWswxceAVbAVbFfjsHHzjK1TZXqJno1qzu7VZV6ju08f7w5fmttvn78ebm4bwzpSGkuIAUNGYBrqXZRzppnoR2t7ZoaBETv2nHWCjRSGXrRAWde5dtCaCmN5e43enrGnFH-uLhe5-LxtoYKLa5b9wNpugPa_RQotF4KwWqTnokkx5-RGeUp-UelBEpCbOXmUmzm5mZMgarat8eZCX_Xi7OOTi6pa-HAuuPoXv7xLMhvvgnHWV29F2uj_xf8DukOtGw</recordid><startdate>20071207</startdate><enddate>20071207</enddate><creator>Athanasiou, Andriani</creator><creator>Clarke, Anna B.</creator><creator>Turner, Amy E.</creator><creator>Kumaran, Nethia M.</creator><creator>Vakilpour, Sara</creator><creator>Smith, Paul A.</creator><creator>Bagiokou, Dimitra</creator><creator>Bradshaw, Tracey D.</creator><creator>Westwell, Andrew D.</creator><creator>Fang, Lin</creator><creator>Lobo, Dileep N.</creator><creator>Constantinescu, Cris S.</creator><creator>Calabrese, Vittorio</creator><creator>Loesch, Andrzej</creator><creator>Alexander, Stephen P.H.</creator><creator>Clothier, Richard H.</creator><creator>Kendall, David A.</creator><creator>Bates, Timothy E.</creator><general>Elsevier Inc</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071207</creationdate><title>Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death</title><author>Athanasiou, Andriani ; Clarke, Anna B. ; Turner, Amy E. ; Kumaran, Nethia M. ; Vakilpour, Sara ; Smith, Paul A. ; Bagiokou, Dimitra ; Bradshaw, Tracey D. ; Westwell, Andrew D. ; Fang, Lin ; Lobo, Dileep N. ; Constantinescu, Cris S. ; Calabrese, Vittorio ; Loesch, Andrzej ; Alexander, Stephen P.H. ; Clothier, Richard H. ; Kendall, David A. ; Bates, Timothy E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-d11c0c1f04b01792774b496fdd64c8841df674594f20869302455e38bb29cd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Anandamide</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Cannabinoid</topic><topic>Cannabinoid Receptor Agonists</topic><topic>Cannabinoids - pharmacology</topic><topic>Carcinoma, Non-Small-Cell Lung</topic><topic>Cell Line, Tumor</topic><topic>Dronabinol - analogs & derivatives</topic><topic>Dronabinol - pharmacology</topic><topic>Electron Transport Complex I - drug effects</topic><topic>Electron Transport Complex II - drug effects</topic><topic>Electron Transport Complex III - drug effects</topic><topic>Endocannabinoids</topic><topic>HU 210</topic><topic>Humans</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Janus</topic><topic>Lung Neoplasms</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - physiology</topic><topic>Models, Biological</topic><topic>Oxygen Consumption - drug effects</topic><topic>Polyunsaturated Alkamides - pharmacology</topic><topic>Δ-9-Tetrahydrocannabinol</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Athanasiou, Andriani</creatorcontrib><creatorcontrib>Clarke, Anna B.</creatorcontrib><creatorcontrib>Turner, Amy E.</creatorcontrib><creatorcontrib>Kumaran, Nethia M.</creatorcontrib><creatorcontrib>Vakilpour, Sara</creatorcontrib><creatorcontrib>Smith, Paul A.</creatorcontrib><creatorcontrib>Bagiokou, Dimitra</creatorcontrib><creatorcontrib>Bradshaw, Tracey D.</creatorcontrib><creatorcontrib>Westwell, Andrew D.</creatorcontrib><creatorcontrib>Fang, Lin</creatorcontrib><creatorcontrib>Lobo, Dileep N.</creatorcontrib><creatorcontrib>Constantinescu, Cris S.</creatorcontrib><creatorcontrib>Calabrese, Vittorio</creatorcontrib><creatorcontrib>Loesch, Andrzej</creatorcontrib><creatorcontrib>Alexander, Stephen P.H.</creatorcontrib><creatorcontrib>Clothier, Richard H.</creatorcontrib><creatorcontrib>Kendall, David A.</creatorcontrib><creatorcontrib>Bates, Timothy E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Athanasiou, Andriani</au><au>Clarke, Anna B.</au><au>Turner, Amy E.</au><au>Kumaran, Nethia M.</au><au>Vakilpour, Sara</au><au>Smith, Paul A.</au><au>Bagiokou, Dimitra</au><au>Bradshaw, Tracey D.</au><au>Westwell, Andrew D.</au><au>Fang, Lin</au><au>Lobo, Dileep N.</au><au>Constantinescu, Cris S.</au><au>Calabrese, Vittorio</au><au>Loesch, Andrzej</au><au>Alexander, Stephen P.H.</au><au>Clothier, Richard H.</au><au>Kendall, David A.</au><au>Bates, Timothy E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2007-12-07</date><risdate>2007</risdate><volume>364</volume><issue>1</issue><spage>131</spage><epage>137</epage><pages>131-137</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Δ-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viability showed that AEA and THC caused significant increases in OD 595
nm at lower concentrations (10–50
μM) and significant decreases at 100
μM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II–III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17931597</pmid><doi>10.1016/j.bbrc.2007.09.107</doi><tpages>7</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2007-12, Vol.364 (1), p.131-137 |
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| subjects | Anandamide Apoptosis Apoptosis - drug effects Arachidonic Acids - pharmacology Cannabinoid Cannabinoid Receptor Agonists Cannabinoids - pharmacology Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Dronabinol - analogs & derivatives Dronabinol - pharmacology Electron Transport Complex I - drug effects Electron Transport Complex II - drug effects Electron Transport Complex III - drug effects Endocannabinoids HU 210 Humans Hydrogen Peroxide - metabolism Janus Lung Neoplasms Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondria - physiology Models, Biological Oxygen Consumption - drug effects Polyunsaturated Alkamides - pharmacology Δ-9-Tetrahydrocannabinol |
| title | Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death |
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