DI Giacomo Silvia, DI Sotto Antonella, Mazzanti Gabriela, Wink Michael
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Anticancer Res. 2017 Mar;37(3):1191-1196. doi: 10.21873/anticanres.11433.
BACKGROUND/AIM: 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.
背景/目的：评估天然倍半萜β-石竹烯（CRY）和氧化β-石竹烯（CRYO）的潜在化学增敏特性。
测试CRY和CRYO对Caco-2、CCRF/CEM和CEM/ADR5000人癌细胞系的细胞毒性。此外，进行联合实验以研究倍半萜增加阿霉素细胞毒性的能力。还通过罗丹明123外排试验研究CRY和CRYO对ATP结合盒（ABC）转运蛋白功能的可能干扰。
尽管细胞毒性较低，但两种物质均能增强阿霉素在所有细胞系中的细胞毒性，其中CRYO是最有效的逆转剂。两种倍半萜还能增加细胞内罗丹明123的含量，这可能是由于抑制了外排泵。
我们的结果突出了CRY和CRYO作为阿霉素化疗新的化学增敏剂以及使耐药癌细胞重新敏感化的潜在作用。
