Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell Syst. 2019 Feb 27;8(2):163-167.e2. doi: 10.1016/j.cels.2019.01.005. Epub 2019 Feb 20.
Although elevated levels of reactive oxygen species (ROS) have been observed in cancer cells and cancer cells aberrantly proliferate, it is not known whether the level of reactive oxygen species and the accumulation of oxidative damage to macromolecules vary across the cell cycle. Here, we measure the prevalence of reactive oxygen species and of biomolecule oxidation across the cell cycle in freely cycling cancer cells. We report that reactive oxygen species vary during the cell cycle and peak in mitosis, resulting in mitotic accumulation of oxidized protein cysteine residues. Prolonged mitotic arrest further increased the levels of ROS and the abundance of oxidatively damaged biomolecules, including cysteine-sulfenic-acid-containing proteins and 8-oxoguanine. These finding suggest that mitotic arrest agents may enhance the effects of ROS-dependent anticancer therapies.
尽管已经观察到癌细胞中活性氧（ROS）水平升高，并且癌细胞异常增殖，但尚不清楚ROS 水平和大分子氧化损伤的积累是否在细胞周期中有所不同。在这里，我们在自由循环的癌细胞中测量整个细胞周期中活性氧和生物分子氧化的普遍性。我们报告说，活性氧在细胞周期中变化，并在有丝分裂中达到峰值，导致有丝分裂中氧化的蛋白质半胱氨酸残基积累。有丝分裂阻滞时间延长进一步增加了 ROS 水平和氧化损伤生物分子的丰度，包括含有半胱氨酸亚磺酸的蛋白质和 8-氧鸟嘌呤。这些发现表明，有丝分裂阻滞剂可能增强 ROS 依赖性抗癌疗法的效果。
