title: β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties.
abstract: Natural bicyclic sesquiterpenes, β-caryophyllene (BCP) and β-caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(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. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2), but not cannabinoid receptor type 1 (CB1). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB1/2binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen-activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 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 CB2may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB1stimulation. Thus, BCP as selective CB2activator 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 BCP, 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 BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.
authors.affiliation: Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolf Weigl, Wroclaw, 53-114, Poland.|The Faculty of Food Science, Department of Chemistry, Wrocław University of Environmental and Life Sciences, 25/27 C.K. Norwida, Wroclaw, 50-375, Poland.
authors.forename: Klaudyna
authors.initials: K
authors.lastname: Fidyt
authors.affiliation: Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolf Weigl, Wroclaw, 53-114, Poland. anna.fiedorowicz@iitd.pan.wroc.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Fiedorowicz
authors.affiliation: Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Rudolf Weigl, Wroclaw, 53-114, Poland.
authors.forename: Leon
authors.initials: L
authors.lastname: Strządała
authors.affiliation: The Faculty of Food Science, Department of Chemistry, Wrocław University of Environmental and Life Sciences, 25/27 C.K. Norwida, Wroclaw, 50-375, Poland.
authors.forename: Antoni
authors.initials: A
authors.lastname: Szumny
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000081223:Polycyclic Sesquiterpenes; D043882:Receptors, Cannabinoid / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000700:Analgesics; D000972:Antineoplastic Agents, Phytogenic; D000081223:Polycyclic Sesquiterpenes; D043882:Receptors, Cannabinoid; D012717:Sesquiterpenes; C024714:caryophyllene; C515179:caryophyllene oxide
keywords: Analgesic; anticancer; antinociception; cannabinoid receptor type 2 (CB2); β-caryophyllene (BCP); β-caryophyllene oxide (BCPO)