Ambrož Martin, Matoušková Petra, Skarka Adam, Zajdlová Martina, Žáková Kateřina, Skálová Lenka
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradecká 1285, 50003 Hradec Králové, Czech Republic.
Molecules. 2017 Jun 20;22(6):1021. doi: 10.3390/molecules22061021.
β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER) and valencene (VAL) are constituents of the essential oil of (MEO), which has significant antiproliferative effect in various cancer cell lines. In the present study, we compared the antiproliferative effect of these sesquiterpenes alone and in combination with the cytostatic drug doxorubicin (DOX) in cancer cell lines with different sensitivity to DOX. Two ovarian cancer cell lines (sensitive A2780 and partly resistant SKOV3) and two lymphoblast cancer cell lines (sensitive CCRF/CEM and completely resistant CEM/ADR) were used. The observed effects varied among sesquiterpenes and also differed in individual cell lines, with only VAL being effective in all the cell lines. A strong synergism of DOX with NER was found in the A2780 cells, while DOX acted synergistically with HUM and CAO in the SKOV3 cells. In the CCRF/CEM cells, a synergism of DOX with CAO and NER was observed. In resistant CEM/ADR cells, sesquiterpenes did not increase DOX efficacy, although they significantly increased accumulation of DOX (up to 10-times) and rhodamine-123 (substrate of efflux transporter ABCB1) within cancer cells. In conclusion, the tested sesquiterpenes were able to improve DOX efficacy in the sensitive and partly resistant cancer cells, but not in cells completely resistant to DOX.
β-石竹烯氧化物（CAO）、α-葎草烯（HUM）、反式橙花叔醇（NER）和瓦伦西亚烯（VAL）是[植物名称未给出]精油的成分，该精油在多种癌细胞系中具有显著的抗增殖作用。在本研究中，我们比较了这些倍半萜单独以及与细胞毒性药物阿霉素（DOX）联合使用时，在对DOX具有不同敏感性的癌细胞系中的抗增殖作用。使用了两种卵巢癌细胞系（敏感的A2780和部分耐药的SKOV3）以及两种淋巴母细胞癌细胞系（敏感的CCRF/CEM和完全耐药的CEM/ADR）。观察到的效应在倍半萜之间各不相同，在各个细胞系中也存在差异，只有VAL在所有细胞系中均有效。在A2780细胞中发现DOX与NER有强烈的协同作用，而在SKOV3细胞中DOX与HUM和CAO协同作用。在CCRF/CEM细胞中，观察到DOX与CAO和NER有协同作用。在耐药的CEM/ADR细胞中，倍半萜虽然显著增加了癌细胞内DOX（高达10倍）和罗丹明-123（外排转运蛋白ABCB1的底物）的蓄积，但并未提高DOX的疗效。总之，所测试的倍半萜能够提高敏感和部分耐药癌细胞中DOX的疗效，但对完全耐药的癌细胞无效。
