Brea-Calvo Gloria, Rodríguez-Hernández Angeles, Fernández-Ayala Daniel J M, Navas Plácido, Sánchez-Alcázar José A
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Carretera de Utrera Km 1, Sevilla, Spain.
Free Radic Biol Med. 2006 Apr 15;40(8):1293-302. doi: 10.1016/j.freeradbiomed.2005.11.014. Epub 2005 Dec 13.
Free radicals have been implicated in the action of many chemotherapeutic drugs. Here we tested the hypothesis that camptothecin and other chemotherapeutic drugs, such as etoposide, doxorubicin, and methotrexate, induce an increase in coenzyme Q(10) levels as part of the antioxidant defense against free radical production under these anticancer treatments in cancer cell lines. Chemotherapy treatment induced both free radical production and an increase in coenzyme Q(10) levels in all the cancer cell lines tested. Reduced coenzyme Q(10) form levels were particularly enhanced. Coenzyme Q(10)-increased levels were associated with up-regulation of COQ genes expression, involved in coenzyme Q(10) biosynthesis. At the translational level, COQ7 protein expression levels were also increased. Furthermore, coenzyme Q(10) biosynthesis inhibition blocked camptothecin-induced coenzyme Q(10) increase, and enhanced camptothecin cytotoxicity. Our findings suggest that coenzyme Q(10) increase is implicated in the cellular defense under chemotherapy treatment and may contribute to cell survival.
自由基与许多化疗药物的作用有关。在此,我们检验了这样一个假设:喜树碱以及其他化疗药物,如依托泊苷、阿霉素和甲氨蝶呤,会使辅酶Q(10)水平升高,这是这些抗癌治疗在癌细胞系中对抗自由基产生的抗氧化防御机制的一部分。化疗处理在所有测试的癌细胞系中均诱导了自由基产生以及辅酶Q(10)水平升高。还原型辅酶Q(10)形式的水平尤其升高。辅酶Q(10)水平升高与参与辅酶Q(10)生物合成的COQ基因表达上调有关。在翻译水平上,COQ7蛋白表达水平也升高。此外,辅酶Q(10)生物合成抑制可阻断喜树碱诱导的辅酶Q(10)升高,并增强喜树碱的细胞毒性。我们的研究结果表明,辅酶Q(10)升高与化疗处理下的细胞防御有关,可能有助于细胞存活。