Laboratory of Bioscience and Biotechnology for Cell Function Control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Japan.
Free Radic Res. 2021 Mar;55(3):211-220. doi: 10.1080/10715762.2021.1902514. Epub 2021 Apr 30.
Many studies have shown that redox regulation is an effective therapeutic strategy for different types of cancer. We have previously demonstrated that combined treatment with dissolved hydrogen molecule (H) and platinum nanocolloid (Pt-nc) has carcinostatic effects and that increased intracellular reactive oxygen species (ROS) levels were closely associated with carcinostatic effects in Ehrlich mouse ascites tumor cells. However, it is unknown whether combined treatment-induced ROS generation can occur in human cancer cells. Therefore, this study aimed to examine the carcinostatic effect of the combined treatment in human cells and investigate the relationship between treatment efficacy and ROS generation. H and Pt-nc treatment could exert cytostatic action by inhibiting the growth of human promyelocytic leukemia HL60 and human gastric adenocarcinoma-derived NUGC-4 cells; however, no effect was observed in normal human embryo fibroblast OUMS-36 cells by the temporary exposure. These findings indicate that combined treatment with H and Pt-nc may act selectively in tumor cells compared with normal cells. Additionally, combined treatment with H and Pt-nc resulted in an approximately 200-fold increase in intracellular ROS levels compared with the control, whereas the suppressive effect of tumor cell growth was abrogated entirely by catalase treatment in NUGC-4 cells. Furthermore, combined treatment with H and Pt-nc induced hydrogen peroxide generation, cellular morphological changes, cell death, and a decline in DNA synthesis-positive cells. In conclusion, combined treatment with H and Pt-nc can induce carcinostatic/carcinocidal effects through intracellular ROS increase, morphological changes, cell death, and DNA synthesis suppression in the human tumor cell line.
许多研究表明，氧化还原调控是治疗不同类型癌症的有效策略。我们之前已经证明，溶解氢分子（H）和铂纳米胶体（Pt-nc）的联合治疗具有抗癌作用，并且细胞内活性氧（ROS）水平的增加与 Ehrlich 小鼠腹水肿瘤细胞的抗癌作用密切相关。然而，尚不清楚联合治疗诱导的 ROS 生成是否会发生在人类癌细胞中。因此，本研究旨在研究联合治疗在人类细胞中的抗癌作用，并探讨治疗效果与 ROS 生成之间的关系。H 和 Pt-nc 治疗可通过抑制人早幼粒细胞白血病 HL60 和人胃腺癌衍生的 NUGC-4 细胞的生长来发挥细胞抑制作用；然而，在正常的人胚胎成纤维细胞 OUMS-36 细胞中，暂时暴露后没有观察到效果。这些发现表明，与正常细胞相比，H 和 Pt-nc 的联合治疗可能在肿瘤细胞中具有选择性作用。此外，与对照组相比，H 和 Pt-nc 的联合治疗导致细胞内 ROS 水平增加了约 200 倍，而在 NUGC-4 细胞中，用 catalase 处理完全消除了对肿瘤细胞生长的抑制作用。此外，H 和 Pt-nc 的联合治疗诱导了过氧化氢的产生、细胞形态的变化、细胞死亡以及 DNA 合成阳性细胞的减少。总之，H 和 Pt-nc 的联合治疗可以通过增加细胞内 ROS、形态变化、细胞死亡和抑制 DNA 合成来诱导人类肿瘤细胞系的抗癌/杀癌作用。
