Chemosensitizing Properties of β-Caryophyllene and β-Caryophyllene Oxide in Combination with Doxorubicin in Human Cancer Cells.
The natural sesquiterpenes β-caryophyllene (CRY) and β-caryophyllene oxide (CRYO) were evaluated for their potential chemosensitizing properties.



CRY and CRYO cytotoxicity was tested against the Caco-2, CCRF/CEM and CEM/ADR5000 human cancer cell lines. Furthermore, combination experiments were carried out in order to study the ability of the sesquiterpenes to increase doxorubicin cytotoxicity. The possible interference of CRY and CRYO with functionality of ATP-binding cassette (ABC)-transporters was also investigated by Rhodamine123 efflux assay.



Despite a low cytotoxicity, both substances were able to enhance the cytotoxicity of doxorubicin in all cell lines, with CRYO being the most effective reversal agent. Both sesquiterpenes were also able to increase the Rho123 content into cells, likely due to inhibition of the efflux pumps.



Our results highlight a potential role of CRY and CRYO as new chemosensitizing agents for doxorubicin chemotherapy and to re-sensitize cancer-resistant cells.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy antonella.disotto@uniroma1.it silvia.digiacomo@uniroma1.it.
Silvia
S
DI Giacomo
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy antonella.disotto@uniroma1.it silvia.digiacomo@uniroma1.it.
Antonella
A
DI Sotto
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Gabriela
G
Mazzanti
Institute of Pharmacy and Molecular Biotechnology - Heidelberg University, Heidelberg, Germany.
Michael
M
Wink
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000737:chemistry*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D000081223:Polycyclic Sesquiterpenes; D020112:Rhodamine 123 / Q000737:chemistry; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry*
D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D020112:Rhodamine 123; D004317:Doxorubicin; C024714:caryophyllene; C515179:caryophyllene oxide
B-caryophyllene; doxorubicin; multidrug resistance; natural compound; sesquiterpenes; β-caryophyllene oxide