Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo
Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camp...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2015-11, Vol.467 (4), p.928-934 |
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| creator | Girola, Natalia Figueiredo, Carlos R. Farias, Camyla F. Azevedo, Ricardo A. Ferreira, Adilson K. Teixeira, Sarah F. Capello, Tabata M. Martins, Euder G.A. Matsuo, Alisson L. Travassos, Luiz R. Lago, João H.G. |
| description | Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca2+ together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy. |
| doi_str_mv | 10.1016/j.bbrc.2015.10.041 |
| format | Article |
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(Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca2+ together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.10.041</identifier><identifier>PMID: 26471302</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Antineoplastic Agents, Phytogenic - therapeutic use ; Antitumor ; Apoptosis ; Apoptosis - drug effects ; Calcium - metabolism ; Calreticulin - metabolism ; Camphene ; Cell Line, Tumor ; Endoplasmic Reticulum - drug effects ; Humans ; Melanoma ; Melanoma, Experimental - drug therapy ; Melanoma, Experimental - pathology ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Piper - chemistry ; Piperaceae ; Terpenes - pharmacology ; Terpenes - therapeutic use</subject><ispartof>Biochemical and biophysical research communications, 2015-11, Vol.467 (4), p.928-934</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-b0a7a6b662c321b7a96a2d4caae5f5429744b808636a3623eae6717875cb4d593</citedby><cites>FETCH-LOGICAL-c389t-b0a7a6b662c321b7a96a2d4caae5f5429744b808636a3623eae6717875cb4d593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2015.10.041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26471302$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Girola, Natalia</creatorcontrib><creatorcontrib>Figueiredo, Carlos R.</creatorcontrib><creatorcontrib>Farias, Camyla F.</creatorcontrib><creatorcontrib>Azevedo, Ricardo A.</creatorcontrib><creatorcontrib>Ferreira, Adilson K.</creatorcontrib><creatorcontrib>Teixeira, Sarah F.</creatorcontrib><creatorcontrib>Capello, Tabata M.</creatorcontrib><creatorcontrib>Martins, Euder G.A.</creatorcontrib><creatorcontrib>Matsuo, Alisson L.</creatorcontrib><creatorcontrib>Travassos, Luiz R.</creatorcontrib><creatorcontrib>Lago, João H.G.</creatorcontrib><title>Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca2+ together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - therapeutic use</subject><subject>Antitumor</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Calcium - metabolism</subject><subject>Calreticulin - metabolism</subject><subject>Camphene</subject><subject>Cell Line, Tumor</subject><subject>Endoplasmic Reticulum - drug effects</subject><subject>Humans</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - pathology</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Piper - chemistry</subject><subject>Piperaceae</subject><subject>Terpenes - pharmacology</subject><subject>Terpenes - therapeutic use</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2q1EAQhRtRvOPVF3AhvbwuMvZP0knAjQz-wQVdKLhrKp0K1pCkY3dnYB7Fnc_ik9lxri7FRVPU4ZxD0R9jT6XYSyHNi-O-64LbKyGrLOxFKe-xnRStKJQU5X22E0KYQrXyyxV7FONRCClL0z5kV8qUtdRC7dj3A0zLV5yRU_QjJOz5EPzEMUacE8HIPeU38I-0YOAOw7yuE7_5vYJDwOec5n51GPNMgeZIjsPil-QjbRqfcITZT5DD4xg5zD3vKS4jnLclUVonHzi4RCdK55z4-eNEJ_-YPRhgjPjkbl6zz29efzq8K24_vH1_eHVbON20qegE1GA6Y5TTSnY1tAZUXzoArIaqVG1dll0jGqMNaKN0vtjUsm7qynVlX7X6mt1cepfgv60Yk50obqfCjH6NVtaVVKJSWv2HVWvZ6lY02aouVhd8jAEHuwSaIJytFHajZ492o2c3epuW6eXQs7v-tZuw_xv5gysbXl4MmD_kRBhsdISzw54CumR7T__q_wV1EK50</recordid><startdate>20151127</startdate><enddate>20151127</enddate><creator>Girola, Natalia</creator><creator>Figueiredo, Carlos R.</creator><creator>Farias, Camyla F.</creator><creator>Azevedo, Ricardo A.</creator><creator>Ferreira, Adilson K.</creator><creator>Teixeira, Sarah F.</creator><creator>Capello, Tabata M.</creator><creator>Martins, Euder G.A.</creator><creator>Matsuo, Alisson L.</creator><creator>Travassos, Luiz R.</creator><creator>Lago, João H.G.</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>7X8</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20151127</creationdate><title>Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo</title><author>Girola, Natalia ; Figueiredo, Carlos R. ; Farias, Camyla F. ; Azevedo, Ricardo A. ; Ferreira, Adilson K. ; Teixeira, Sarah F. ; Capello, Tabata M. ; Martins, Euder G.A. ; Matsuo, Alisson L. ; Travassos, Luiz R. ; Lago, João H.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-b0a7a6b662c321b7a96a2d4caae5f5429744b808636a3623eae6717875cb4d593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - therapeutic use</topic><topic>Antitumor</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Calcium - metabolism</topic><topic>Calreticulin - metabolism</topic><topic>Camphene</topic><topic>Cell Line, Tumor</topic><topic>Endoplasmic Reticulum - drug effects</topic><topic>Humans</topic><topic>Melanoma</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Melanoma, Experimental - pathology</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Piper - chemistry</topic><topic>Piperaceae</topic><topic>Terpenes - pharmacology</topic><topic>Terpenes - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Girola, Natalia</creatorcontrib><creatorcontrib>Figueiredo, Carlos R.</creatorcontrib><creatorcontrib>Farias, Camyla F.</creatorcontrib><creatorcontrib>Azevedo, Ricardo A.</creatorcontrib><creatorcontrib>Ferreira, Adilson K.</creatorcontrib><creatorcontrib>Teixeira, Sarah F.</creatorcontrib><creatorcontrib>Capello, Tabata M.</creatorcontrib><creatorcontrib>Martins, Euder G.A.</creatorcontrib><creatorcontrib>Matsuo, Alisson L.</creatorcontrib><creatorcontrib>Travassos, Luiz R.</creatorcontrib><creatorcontrib>Lago, João H.G.</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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Girola, Natalia</au><au>Figueiredo, Carlos R.</au><au>Farias, Camyla F.</au><au>Azevedo, Ricardo A.</au><au>Ferreira, Adilson K.</au><au>Teixeira, Sarah F.</au><au>Capello, Tabata M.</au><au>Martins, Euder G.A.</au><au>Matsuo, Alisson L.</au><au>Travassos, Luiz R.</au><au>Lago, João H.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-11-27</date><risdate>2015</risdate><volume>467</volume><issue>4</issue><spage>928</spage><epage>934</epage><pages>928-934</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. 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| subjects | Animals Antineoplastic Agents, Phytogenic - pharmacology Antineoplastic Agents, Phytogenic - therapeutic use Antitumor Apoptosis Apoptosis - drug effects Calcium - metabolism Calreticulin - metabolism Camphene Cell Line, Tumor Endoplasmic Reticulum - drug effects Humans Melanoma Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Membrane Potential, Mitochondrial - drug effects Mice Piper - chemistry Piperaceae Terpenes - pharmacology Terpenes - therapeutic use |
| title | Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo |
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