Yokoyama Chikako, Sueyoshi Yuto, Ema Mika, Mori Yumi, Takaishi Kazuto, Hisatomi Hisashi
Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
Laboratory of Cellular and Molecular Biochemistry, Department of Materials and Life Sciences, Seikei University, Musashino, Tokyo 180-8633, Japan.
Oncol Lett. 2017 Nov;14(5):6066-6070. doi: 10.3892/ol.2017.6931. Epub 2017 Sep 14.
Reactive oxygen species (ROS) are generated in the cell through multiple mechanisms. Intracellular ROS are rapidly detoxified by various enzymatic and non-enzymatic mechanisms; however, disruption of the oxidant-antioxidant balance causes oxidative stress and elicits cell damage. The oxidative stress induced by chemotherapy is known to cause side effects in patients with cancer. However, few studies have examined whether anticancer drugs induce oxidative stress in cancer cells. Furthermore, the precise mechanism by which anticancer drugs induce the generation of ROS remains unclear. In the present study, to investigate whether anticancer drugs induce oxidative stress, DLD-1 human colorectal cancer cells were treated with 20 different anticancer drugs and then stained with CellROX ROS detection reagent. Furthermore, an oxygen radical absorbance capacity assay in the presence of copper was performed to estimate the oxidative activities of the anticancer drugs in the absence of cells. The data of the present study using assay methods in the presence and absence of cells suggest that nimustine, actinomycin D, doxorubicin, mitomycin C, mitoxantrone, carmofur, gemcitabine, mercaptopurine, camptothecin, paclitaxel, vinblastine, and vinorelbine are able to induce oxidative stress.
活性氧（ROS）通过多种机制在细胞内产生。细胞内的ROS通过各种酶促和非酶促机制迅速解毒；然而，氧化还原抗氧化剂平衡的破坏会导致氧化应激并引发细胞损伤。已知化疗诱导的氧化应激会在癌症患者中引起副作用。然而，很少有研究探讨抗癌药物是否会在癌细胞中诱导氧化应激。此外，抗癌药物诱导ROS产生的确切机制仍不清楚。在本研究中，为了研究抗癌药物是否会诱导氧化应激，用20种不同的抗癌药物处理DLD-1人结肠癌细胞，然后用CellROX ROS检测试剂染色。此外，在存在铜的情况下进行氧自由基吸收能力测定，以估计在无细胞情况下抗癌药物的氧化活性。本研究使用有细胞和无细胞检测方法的数据表明，尼莫司汀、放线菌素D、多柔比星、丝裂霉素C、米托蒽醌、卡莫氟、吉西他滨、巯嘌呤、喜树碱、紫杉醇、长春碱和长春瑞滨能够诱导氧化应激。
