Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville FL 32224, USA.
Free Radic Res. 2010 May;44(5):479-96. doi: 10.3109/10715761003667554.
Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.
活性氧 (ROS) 的水平在几乎所有的癌症中都有所升高,它们促进了肿瘤发展和进展的许多方面。然而,肿瘤细胞也表达了更高水平的抗氧化蛋白来清除 ROS,这表明细胞内 ROS 水平需要保持微妙的平衡,以维持癌细胞的功能。此外,生成的自由基、其生成的位置以及局部浓度对于 ROS 在癌症中的细胞功能都很重要。对于新的治疗策略来说,一个挑战将是精细地调节细胞内的 ROS 信号,以有效地剥夺细胞免受 ROS 诱导的肿瘤促进事件,从而使平衡向 ROS 诱导的凋亡信号倾斜。或者,治疗性抗氧化剂可以阻止肿瘤发展早期的 ROS 重要事件。然而,为了有效地靶向特定的 ROS 感应信号通路,需要确定这些信号通路在调节肿瘤细胞中的多样性应激相关的细胞功能。这篇综述讨论了肿瘤细胞内 ROS 的生成、解毒、细胞效应,以及它们利用的主要信号级联,但也展望了它们在治疗中的调节。