Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species

Background The endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results s...

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Veröffentlicht in:Head & neck 2015-08, Vol.37 (8), p.1187-1192
Hauptverfasser: Park, Seok-Woo, Kim, Ji-Eun, Oh, Sang-Mi, Cha, Won-Jae, Hah, Jeong-Hun, Sung, Myung-Whun
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container_end_page 1192
container_issue 8
container_start_page 1187
container_title Head & neck
container_volume 37
creator Park, Seok-Woo
Kim, Ji-Eun
Oh, Sang-Mi
Cha, Won-Jae
Hah, Jeong-Hun
Sung, Myung-Whun
description Background The endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2‐AG did not. The anticancer effect of AEA seemed to be mediated by a receptor‐independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA‐dependent inhibition of cell proliferation. We found that cyclooxygenase‐2 (COX‐2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA‐dependent inhibition of cell proliferation. Conclusion These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor‐independent mechanism. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1187–1192, 2015
doi_str_mv 10.1002/hed.23727
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In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2‐AG did not. The anticancer effect of AEA seemed to be mediated by a receptor‐independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA‐dependent inhibition of cell proliferation. We found that cyclooxygenase‐2 (COX‐2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA‐dependent inhibition of cell proliferation. Conclusion These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor‐independent mechanism. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1187–1192, 2015</description><identifier>ISSN: 1043-3074</identifier><identifier>EISSN: 1097-0347</identifier><identifier>DOI: 10.1002/hed.23727</identifier><identifier>PMID: 24797795</identifier><identifier>CODEN: HEANEE</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>anandamide ; anticancer agents ; Antineoplastic Agents - pharmacology ; Arachidonic Acids - pharmacology ; Cannabinoid Receptor Agonists - pharmacology ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; endocannabinoids ; Endocannabinoids - pharmacology ; Glycerides - pharmacology ; head and neck cancer ; Head and Neck Neoplasms - drug therapy ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Humans ; Polyunsaturated Alkamides - pharmacology ; reactive oxygen species ; Reactive Oxygen Species - metabolism</subject><ispartof>Head &amp; neck, 2015-08, Vol.37 (8), p.1187-1192</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5607-c145cca39b71c419f4585600c9f125b5f34011fa092f0ccb16e2e331625d04d93</citedby><cites>FETCH-LOGICAL-c5607-c145cca39b71c419f4585600c9f125b5f34011fa092f0ccb16e2e331625d04d93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhed.23727$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhed.23727$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24797795$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Seok-Woo</creatorcontrib><creatorcontrib>Kim, Ji-Eun</creatorcontrib><creatorcontrib>Oh, Sang-Mi</creatorcontrib><creatorcontrib>Cha, Won-Jae</creatorcontrib><creatorcontrib>Hah, Jeong-Hun</creatorcontrib><creatorcontrib>Sung, Myung-Whun</creatorcontrib><title>Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species</title><title>Head &amp; neck</title><addtitle>Head Neck</addtitle><description>Background The endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2‐AG did not. The anticancer effect of AEA seemed to be mediated by a receptor‐independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA‐dependent inhibition of cell proliferation. We found that cyclooxygenase‐2 (COX‐2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA‐dependent inhibition of cell proliferation. Conclusion These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor‐independent mechanism. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1187–1192, 2015</description><subject>anandamide</subject><subject>anticancer agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Cannabinoid Receptor Agonists - pharmacology</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>endocannabinoids</subject><subject>Endocannabinoids - pharmacology</subject><subject>Glycerides - pharmacology</subject><subject>head and neck cancer</subject><subject>Head and Neck Neoplasms - drug therapy</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Polyunsaturated Alkamides - pharmacology</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><issn>1043-3074</issn><issn>1097-0347</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQhy0EoqVw4AWQJS5wSOt_idfHqpQtqIILCG6WdzJm3W6c1E5K9zV4YpxulwMS4hLH428-e_Qj5CVnx5wxcbLG9lhILfQjcsiZ0RWTSj-e_5WsJNPqgDzL-YoxJhslnpIDobTR2tSH5NdpHAO4CJgoeo8wZtp76qKLretCi7SPdI2uLaWWRoRrmm8m1_VTpoCbDQWXIMS-c_fbTG-Do-Ma6ZD6doIxlPbiSwg4jH2qQmxxwPKJYym6AtyWK-62PzDSPCAEzM_JE-82GV88rEfk6_vzL2cX1eXn5Yez08sK6obpCriqAZw0K81BceNVvSgHDIznol7VXirGuXfMCM8AVrxBgVLyRtQtU62RR-TNzlueejNhHm0X8jyEi1jGs3zBDVeyOP-PNkYLvljUs_X1X-hVP6VYBpmphikmuSjU2x0Fqc85obdDCp1LW8uZnTO1JVN7n2lhXz0Yp1VXqntyH2IBTnbAz7DB7b9N9uL83V5Z7TpCHvHuT4dL17bRUtf226elVcrI5uP3pZXyN0T7ulY</recordid><startdate>201508</startdate><enddate>201508</enddate><creator>Park, Seok-Woo</creator><creator>Kim, Ji-Eun</creator><creator>Oh, Sang-Mi</creator><creator>Cha, Won-Jae</creator><creator>Hah, Jeong-Hun</creator><creator>Sung, Myung-Whun</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201508</creationdate><title>Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species</title><author>Park, Seok-Woo ; Kim, Ji-Eun ; Oh, Sang-Mi ; Cha, Won-Jae ; Hah, Jeong-Hun ; Sung, Myung-Whun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5607-c145cca39b71c419f4585600c9f125b5f34011fa092f0ccb16e2e331625d04d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>anandamide</topic><topic>anticancer agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Cannabinoid Receptor Agonists - pharmacology</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Line, Tumor</topic><topic>endocannabinoids</topic><topic>Endocannabinoids - pharmacology</topic><topic>Glycerides - pharmacology</topic><topic>head and neck cancer</topic><topic>Head and Neck Neoplasms - drug therapy</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Polyunsaturated Alkamides - pharmacology</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Seok-Woo</creatorcontrib><creatorcontrib>Kim, Ji-Eun</creatorcontrib><creatorcontrib>Oh, Sang-Mi</creatorcontrib><creatorcontrib>Cha, Won-Jae</creatorcontrib><creatorcontrib>Hah, Jeong-Hun</creatorcontrib><creatorcontrib>Sung, Myung-Whun</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Head &amp; neck</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Seok-Woo</au><au>Kim, Ji-Eun</au><au>Oh, Sang-Mi</au><au>Cha, Won-Jae</au><au>Hah, Jeong-Hun</au><au>Sung, Myung-Whun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species</atitle><jtitle>Head &amp; neck</jtitle><addtitle>Head Neck</addtitle><date>2015-08</date><risdate>2015</risdate><volume>37</volume><issue>8</issue><spage>1187</spage><epage>1192</epage><pages>1187-1192</pages><issn>1043-3074</issn><eissn>1097-0347</eissn><coden>HEANEE</coden><abstract>Background The endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2‐AG did not. The anticancer effect of AEA seemed to be mediated by a receptor‐independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA‐dependent inhibition of cell proliferation. We found that cyclooxygenase‐2 (COX‐2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA‐dependent inhibition of cell proliferation. Conclusion These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor‐independent mechanism. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1187–1192, 2015</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24797795</pmid><doi>10.1002/hed.23727</doi><tpages>6</tpages></addata></record>
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subjects anandamide
anticancer agents
Antineoplastic Agents - pharmacology
Arachidonic Acids - pharmacology
Cannabinoid Receptor Agonists - pharmacology
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Line, Tumor
endocannabinoids
Endocannabinoids - pharmacology
Glycerides - pharmacology
head and neck cancer
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Humans
Polyunsaturated Alkamides - pharmacology
reactive oxygen species
Reactive Oxygen Species - metabolism
title Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species
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