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Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells
Geraniol, a natural component of plant essential oils, has antiproliferative effects on human colon cancer cells. To obtain more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of proteins involved in cell signaling pathways. Since...
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| Published in: | The Journal of pharmacology and experimental therapeutics 2002-11, Vol.303 (2), p.711-715 |
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| container_end_page | 715 |
| container_issue | 2 |
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| container_title | The Journal of pharmacology and experimental therapeutics |
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| creator | Carnesecchi, S Bradaia, A Fischer, B Coelho, D Schöller-Guinard, M Gosse, F Raul, F |
| description | Geraniol, a natural component of plant essential oils, has antiproliferative effects on human colon cancer cells. To obtain
more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of
proteins involved in cell signaling pathways. Since geraniol is a well known inhibitor of mevalonate metabolism, the effect
of mevalonate supplementation on geraniol-triggered growth inhibition was also determined. Geraniol (400 μM) induced membrane
depolarization with a decrease of membrane resistance due to local perforation of the cell membrane. Incubation of Caco-2
cells with geraniol (400 μM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity. After 16 h of incubation,
geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK). Mevalonate
supplementation did not reverse inhibition of cell growth by geraniol. These results indicate that the antiproliferative effect
of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation
of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms. |
| doi_str_mv | 10.1124/jpet.102.039263 |
| format | article |
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more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of
proteins involved in cell signaling pathways. Since geraniol is a well known inhibitor of mevalonate metabolism, the effect
of mevalonate supplementation on geraniol-triggered growth inhibition was also determined. Geraniol (400 μM) induced membrane
depolarization with a decrease of membrane resistance due to local perforation of the cell membrane. Incubation of Caco-2
cells with geraniol (400 μM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity. After 16 h of incubation,
geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK). Mevalonate
supplementation did not reverse inhibition of cell growth by geraniol. These results indicate that the antiproliferative effect
of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation
of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms.</description><identifier>ISSN: 0022-3565</identifier><identifier>EISSN: 1521-0103</identifier><identifier>DOI: 10.1124/jpet.102.039263</identifier><identifier>PMID: 12388655</identifier><language>eng</language><publisher>United States: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Blotting, Western ; Caco-2 Cells ; Cell Division - drug effects ; Cell Membrane - drug effects ; Cell Membrane Permeability - drug effects ; Electrophysiology ; Humans ; Membrane Potentials - drug effects ; Mevalonic Acid - pharmacology ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases - metabolism ; Patch-Clamp Techniques ; Protein Kinase C - physiology ; Signal Transduction - drug effects ; Terpenes - pharmacology</subject><ispartof>The Journal of pharmacology and experimental therapeutics, 2002-11, Vol.303 (2), p.711-715</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-d57e6d0781419c6c61f6106b24314b62f0b3c80e1cd05939124386826b3593d73</citedby><cites>FETCH-LOGICAL-c390t-d57e6d0781419c6c61f6106b24314b62f0b3c80e1cd05939124386826b3593d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12388655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carnesecchi, S</creatorcontrib><creatorcontrib>Bradaia, A</creatorcontrib><creatorcontrib>Fischer, B</creatorcontrib><creatorcontrib>Coelho, D</creatorcontrib><creatorcontrib>Schöller-Guinard, M</creatorcontrib><creatorcontrib>Gosse, F</creatorcontrib><creatorcontrib>Raul, F</creatorcontrib><title>Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells</title><title>The Journal of pharmacology and experimental therapeutics</title><addtitle>J Pharmacol Exp Ther</addtitle><description>Geraniol, a natural component of plant essential oils, has antiproliferative effects on human colon cancer cells. To obtain
more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of
proteins involved in cell signaling pathways. Since geraniol is a well known inhibitor of mevalonate metabolism, the effect
of mevalonate supplementation on geraniol-triggered growth inhibition was also determined. Geraniol (400 μM) induced membrane
depolarization with a decrease of membrane resistance due to local perforation of the cell membrane. Incubation of Caco-2
cells with geraniol (400 μM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity. After 16 h of incubation,
geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK). Mevalonate
supplementation did not reverse inhibition of cell growth by geraniol. These results indicate that the antiproliferative effect
of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation
of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms.</description><subject>Blotting, Western</subject><subject>Caco-2 Cells</subject><subject>Cell Division - drug effects</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Electrophysiology</subject><subject>Humans</subject><subject>Membrane Potentials - drug effects</subject><subject>Mevalonic Acid - pharmacology</subject><subject>Mitogen-Activated Protein Kinase 3</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Patch-Clamp Techniques</subject><subject>Protein Kinase C - physiology</subject><subject>Signal Transduction - drug effects</subject><subject>Terpenes - pharmacology</subject><issn>0022-3565</issn><issn>1521-0103</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNpFkMtPxCAQh4nR6Po4ezOcvHWdgZa2R9P4SjSaqGcClO5i-lihzab_vehu4onMzI8P5iPkEmGJyNKbr40dlwhsCbxkgh-QBWYME0Dgh2QBwFjCM5GdkNMQvgAwTQU_JifIeFGILFuQ8Gb9OHmtRjf0VM_0wXrVu6GlQ0Mr27b0xXY6tiyNyc4q7Vo3zlT1NX13q1619CNOQz2ZP8KbGtdbNQfqevo4daqn1dDGfqV6Y_0fMZyTo0a1wV7szzPyeX_3UT0mz68PT9Xtc2J4CWNSZ7kVNeQFplgaYQQ2AkFolnJMtWANaG4KsGhqyEpeRh-8EAUTmseyzvkZud5xN374nmwYZeeCiT-I2wxTkDnDMqJFDN7sgsYPIXjbyI13nfKzRJC_nuWv51gwufMcb1zt0ZPubP2f34v9f3vtVuut81Zu1sp3ykQbq1ly4JLJHJH_AE5Qhhs</recordid><startdate>20021101</startdate><enddate>20021101</enddate><creator>Carnesecchi, S</creator><creator>Bradaia, A</creator><creator>Fischer, B</creator><creator>Coelho, D</creator><creator>Schöller-Guinard, M</creator><creator>Gosse, F</creator><creator>Raul, F</creator><general>American Society for Pharmacology and Experimental Therapeutics</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>7X8</scope></search><sort><creationdate>20021101</creationdate><title>Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells</title><author>Carnesecchi, S ; Bradaia, A ; Fischer, B ; Coelho, D ; Schöller-Guinard, M ; Gosse, F ; Raul, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-d57e6d0781419c6c61f6106b24314b62f0b3c80e1cd05939124386826b3593d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Blotting, Western</topic><topic>Caco-2 Cells</topic><topic>Cell Division - drug effects</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane Permeability - drug effects</topic><topic>Electrophysiology</topic><topic>Humans</topic><topic>Membrane Potentials - drug effects</topic><topic>Mevalonic Acid - pharmacology</topic><topic>Mitogen-Activated Protein Kinase 3</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Patch-Clamp Techniques</topic><topic>Protein Kinase C - physiology</topic><topic>Signal Transduction - drug effects</topic><topic>Terpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carnesecchi, S</creatorcontrib><creatorcontrib>Bradaia, A</creatorcontrib><creatorcontrib>Fischer, B</creatorcontrib><creatorcontrib>Coelho, D</creatorcontrib><creatorcontrib>Schöller-Guinard, M</creatorcontrib><creatorcontrib>Gosse, F</creatorcontrib><creatorcontrib>Raul, F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pharmacology and experimental therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carnesecchi, S</au><au>Bradaia, A</au><au>Fischer, B</au><au>Coelho, D</au><au>Schöller-Guinard, M</au><au>Gosse, F</au><au>Raul, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells</atitle><jtitle>The Journal of pharmacology and experimental therapeutics</jtitle><addtitle>J Pharmacol Exp Ther</addtitle><date>2002-11-01</date><risdate>2002</risdate><volume>303</volume><issue>2</issue><spage>711</spage><epage>715</epage><pages>711-715</pages><issn>0022-3565</issn><eissn>1521-0103</eissn><abstract>Geraniol, a natural component of plant essential oils, has antiproliferative effects on human colon cancer cells. To obtain
more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of
proteins involved in cell signaling pathways. Since geraniol is a well known inhibitor of mevalonate metabolism, the effect
of mevalonate supplementation on geraniol-triggered growth inhibition was also determined. Geraniol (400 μM) induced membrane
depolarization with a decrease of membrane resistance due to local perforation of the cell membrane. Incubation of Caco-2
cells with geraniol (400 μM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity. After 16 h of incubation,
geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK). Mevalonate
supplementation did not reverse inhibition of cell growth by geraniol. These results indicate that the antiproliferative effect
of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation
of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms.</abstract><cop>United States</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>12388655</pmid><doi>10.1124/jpet.102.039263</doi><tpages>5</tpages></addata></record> |
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| ispartof | The Journal of pharmacology and experimental therapeutics, 2002-11, Vol.303 (2), p.711-715 |
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| source | Medical Journals (Open access) |
| subjects | Blotting, Western Caco-2 Cells Cell Division - drug effects Cell Membrane - drug effects Cell Membrane Permeability - drug effects Electrophysiology Humans Membrane Potentials - drug effects Mevalonic Acid - pharmacology Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases - metabolism Patch-Clamp Techniques Protein Kinase C - physiology Signal Transduction - drug effects Terpenes - pharmacology |
| title | Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells |
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