In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani
Cedrus libani is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce C. libani oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen...
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| creator | Elias, Andree Shebaby, Wassim N. Nehme, Bilal Faour, Wissam Bassil, Bassem S. Hakim, Joelle El Iskandar, Rita Dib-Jalbout, Nahia Mroueh, Mohamad Daher, Costantine Taleb, Robin I. |
| description | Cedrus libani
is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce
C. libani
oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC
50
8.1 μg/mL) and colon (HT-29, IC
50
10.1 μg/mL; Caco-2, IC
50
9.9 μg/mL) with ovarian (Sk-OV-3, IC
50
> 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy. |
| doi_str_mv | 10.1038/s41598-019-49374-9 |
| format | Article |
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is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce
C. libani
oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC
50
8.1 μg/mL) and colon (HT-29, IC
50
10.1 μg/mL; Caco-2, IC
50
9.9 μg/mL) with ovarian (Sk-OV-3, IC
50
> 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-49374-9</identifier><identifier>PMID: 31492934</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/2 ; 13/31 ; 631/154/570 ; 631/67/1059/99 ; 64/60 ; 82/16 ; 82/58 ; 82/6 ; Animals ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; Antineoplastic Agents, Phytogenic - chemistry ; Antineoplastic Agents, Phytogenic - pharmacology ; Caco-2 Cells ; Cancer ; Cedrus - chemistry ; Cedrus libani ; Cell Line, Tumor ; Cell Survival - drug effects ; Cells, Cultured ; Cisplatin ; Colon ; Column chromatography ; Crystallography ; Cyclooxygenase-2 ; Cytotoxicity ; Edema ; Edema - prevention & control ; Hindlimb - drug effects ; Hindlimb - pathology ; HT29 Cells ; Humanities and Social Sciences ; Humans ; Inflammation ; Lipopolysaccharides ; Magnetic resonance spectroscopy ; Male ; Molecular Structure ; Monocytes ; multidisciplinary ; NMR ; Nuclear magnetic resonance ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Rats, Sprague-Dawley ; Science ; Science (multidisciplinary) ; Tumor cell lines ; X-ray crystallography</subject><ispartof>Scientific reports, 2019-09, Vol.9 (1), p.12855-9, Article 12855</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-1ade0f7b935abfa942408a08af995cb0ee387c34a8f6b7312db87ed15e1f44cc3</citedby><cites>FETCH-LOGICAL-c474t-1ade0f7b935abfa942408a08af995cb0ee387c34a8f6b7312db87ed15e1f44cc3</cites><orcidid>0000-0002-0746-3687 ; 0000-0001-8033-6951</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731217/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731217/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31492934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elias, Andree</creatorcontrib><creatorcontrib>Shebaby, Wassim N.</creatorcontrib><creatorcontrib>Nehme, Bilal</creatorcontrib><creatorcontrib>Faour, Wissam</creatorcontrib><creatorcontrib>Bassil, Bassem S.</creatorcontrib><creatorcontrib>Hakim, Joelle El</creatorcontrib><creatorcontrib>Iskandar, Rita</creatorcontrib><creatorcontrib>Dib-Jalbout, Nahia</creatorcontrib><creatorcontrib>Mroueh, Mohamad</creatorcontrib><creatorcontrib>Daher, Costantine</creatorcontrib><creatorcontrib>Taleb, Robin I.</creatorcontrib><title>In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Cedrus libani
is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce
C. libani
oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC
50
8.1 μg/mL) and colon (HT-29, IC
50
10.1 μg/mL; Caco-2, IC
50
9.9 μg/mL) with ovarian (Sk-OV-3, IC
50
> 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.</description><subject>13/106</subject><subject>13/2</subject><subject>13/31</subject><subject>631/154/570</subject><subject>631/67/1059/99</subject><subject>64/60</subject><subject>82/16</subject><subject>82/58</subject><subject>82/6</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - chemistry</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Caco-2 Cells</subject><subject>Cancer</subject><subject>Cedrus - chemistry</subject><subject>Cedrus libani</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cisplatin</subject><subject>Colon</subject><subject>Column chromatography</subject><subject>Crystallography</subject><subject>Cyclooxygenase-2</subject><subject>Cytotoxicity</subject><subject>Edema</subject><subject>Edema - 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Academic</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>Elias, Andree</au><au>Shebaby, Wassim N.</au><au>Nehme, Bilal</au><au>Faour, Wissam</au><au>Bassil, Bassem S.</au><au>Hakim, Joelle El</au><au>Iskandar, Rita</au><au>Dib-Jalbout, Nahia</au><au>Mroueh, Mohamad</au><au>Daher, Costantine</au><au>Taleb, Robin I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-09-06</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>12855</spage><epage>9</epage><pages>12855-9</pages><artnum>12855</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Cedrus libani
is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce
C. libani
oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC
50
8.1 μg/mL) and colon (HT-29, IC
50
10.1 μg/mL; Caco-2, IC
50
9.9 μg/mL) with ovarian (Sk-OV-3, IC
50
> 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31492934</pmid><doi>10.1038/s41598-019-49374-9</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0746-3687</orcidid><orcidid>https://orcid.org/0000-0001-8033-6951</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2019-09, Vol.9 (1), p.12855-9, Article 12855 |
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| language | eng |
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| source | MEDLINE; 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 | 13/106 13/2 13/31 631/154/570 631/67/1059/99 64/60 82/16 82/58 82/6 Animals Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacology Caco-2 Cells Cancer Cedrus - chemistry Cedrus libani Cell Line, Tumor Cell Survival - drug effects Cells, Cultured Cisplatin Colon Column chromatography Crystallography Cyclooxygenase-2 Cytotoxicity Edema Edema - prevention & control Hindlimb - drug effects Hindlimb - pathology HT29 Cells Humanities and Social Sciences Humans Inflammation Lipopolysaccharides Magnetic resonance spectroscopy Male Molecular Structure Monocytes multidisciplinary NMR Nuclear magnetic resonance Plant Extracts - chemistry Plant Extracts - pharmacology Rats, Sprague-Dawley Science Science (multidisciplinary) Tumor cell lines X-ray crystallography |
| title | In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T01%3A11%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20Vitro%20and%20In%20Vivo%20Evaluation%20of%20the%20Anticancer%20and%20Anti-inflammatory%20Activities%20of%202-Himachelen-7-ol%20isolated%20from%20Cedrus%20Libani&rft.jtitle=Scientific%20reports&rft.au=Elias,%20Andree&rft.date=2019-09-06&rft.volume=9&rft.issue=1&rft.spage=12855&rft.epage=9&rft.pages=12855-9&rft.artnum=12855&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-019-49374-9&rft_dat=%3Cproquest_pubme%3E2285700763%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2285700763&rft_id=info:pmid/31492934&rfr_iscdi=true |