Gill Jennifer G, Piskounova Elena, Morrison Sean J
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
Department of Pediatrics, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
Cold Spring Harb Symp Quant Biol. 2016;81:163-175. doi: 10.1101/sqb.2016.81.030791. Epub 2017 Jan 12.
Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.
活性氧（ROS）是一类高反应性分子，源自多种细胞来源，包括线粒体中的氧化代谢。在低水平时，它们对细胞可能有益，可激活促进增殖或存活的信号通路。在高水平时，ROS可通过氧化蛋白质、脂质和核酸来损伤或杀死细胞。据推测，抗氧化剂可能通过降低ROS诱导的突变率和延缓癌症发生而使高危患者受益。然而，在临床试验中，抗氧化剂的膳食补充通常已被证明无效或有害。在癌症发生和进展的某些阶段，高ROS水平会限制癌细胞的存活。在这些时期，抗氧化剂的膳食补充可能会促进癌细胞存活和癌症进展。这就提出了一种可能性，即不应使用抗氧化剂治疗癌症患者，而应使用加剧氧化应激或阻断赋予氧化应激抗性的代谢适应的促氧化剂来治疗他们。
