{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:20:25Z","timestamp":1792120825895,"version":"4.4.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Committee for Scientific Research, Warsaw, Poland","award":["3\/2016"],"award-info":[{"award-number":["3\/2016"]}]},{"name":"Wroclaw Centre of Biotechnology"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Abstract<\/jats:title>\n \n Natural bicyclic sesquiterpenes,\n \u03b2<\/jats:italic>\n \u2010caryophyllene (\n BCP<\/jats:styled-content>\n ) and\n \u03b2<\/jats:italic>\n \u2010caryophyllene oxide (\n BCPO<\/jats:styled-content>\n ), are present in a large number of plants worldwide. Both\n BCP<\/jats:styled-content>\n and\n BCPO<\/jats:styled-content>\n (\n BCP<\/jats:styled-content>\n (O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described.\n BCP<\/jats:styled-content>\n is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (\n CB<\/jats:styled-content>\n 2<\/jats:sub>\n ), but not cannabinoid receptor type 1 (\n CB<\/jats:styled-content>\n 1<\/jats:sub>\n ). In opposite,\n BCP<\/jats:styled-content>\n oxidation derivative,\n BCPO<\/jats:styled-content>\n , does not exhibit\n CB<\/jats:styled-content>\n 1\/2<\/jats:sub>\n binding, thus the mechanism of its action is not related to endocannabinoid system (\n ECS<\/jats:styled-content>\n ) machinery. It is known that\n BCPO<\/jats:styled-content>\n alters several key pathways for cancer development, such as mitogen\u2010activated protein kinase (\n MAPK<\/jats:styled-content>\n ),\n PI<\/jats:styled-content>\n 3K\/\n AKT<\/jats:styled-content>\n \/\n mTOR<\/jats:styled-content>\n \/S6K1 and\n STAT<\/jats:styled-content>\n 3 pathways. In addition, treatment with this compound reduces the expression of procancer genes\/proteins, while increases the levels of those with proapoptotic properties. The selective activation of\n CB<\/jats:styled-content>\n 2<\/jats:sub>\n may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with\n CB<\/jats:styled-content>\n 1<\/jats:sub>\n stimulation. Thus,\n BCP<\/jats:styled-content>\n as selective\n CB<\/jats:styled-content>\n 2<\/jats:sub>\n activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of\n BCP<\/jats:styled-content>\n , anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of\n BCP<\/jats:styled-content>\n and\n BCPO<\/jats:styled-content>\n , the mechanisms of their actions, and potential therapeutic utility.\n <\/jats:p>","DOI":"10.1002\/cam4.816","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T05:39:32Z","timestamp":1475818772000},"page":"3007-3017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":639,"title":["\u03b2<\/i>\n \u2010caryophyllene and\n \u03b2<\/i>\n \u2010caryophyllene oxide\u2014natural compounds of anticancer and analgesic properties"],"prefix":"10.1002","volume":"5","author":[{"given":"Klaudyna","family":"Fidyt","sequence":"first","affiliation":[{"name":"Laboratory of Tumor Molecular Immunobiology Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences 12 Rudolf Weigl Wroclaw 53\u2010114 Poland"},{"name":"The Faculty of Food Science Department of Chemistry Wroc\u0142aw University of Environmental and Life Sciences 25\/27 C.K. Norwida Wroclaw 50\u2010375 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Fiedorowicz","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Molecular Immunobiology Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences 12 Rudolf Weigl Wroclaw 53\u2010114 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Strz\u0105da\u0142a","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Molecular Immunobiology Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences 12 Rudolf Weigl Wroclaw 53\u2010114 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Szumny","sequence":"additional","affiliation":[{"name":"The Faculty of Food Science Department of Chemistry Wroc\u0142aw University of Environmental and Life Sciences 25\/27 C.K. Norwida Wroclaw 50\u2010375 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tca.2014.11.029"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707270"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2014.04.018"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2006.08.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0518610"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.10.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2007.07.050"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules201119707"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50085a029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.31254\/jsir.2014.3110"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498258609043566"},{"key":"e_1_2_9_13_1","first-page":"1971","article-title":"Acute oral toxicity studies in rats, acute dermal toxicity and primary skin irritation studies in rabbits of 17 fragrance materials","volume":"30","author":"Hart E.","year":"1971","journal-title":"Bionetics Res. 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