活性氧在癌症治疗中的药理学调节

Title:Pharmacological Modulation of Reactive Oxygen Species in Cancer Treatment

Volume: 16 Issue: 1

Author(s): Judit Ribas, Paolo Mattiolo and Jacint Boix

Affiliation:

关键词: 细胞死亡，细胞实验药理，丁硫氨酸，Mdivi-1，氧化应激，p53

摘要: Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen species (ROS). To cope with this toxicity, evolution provided cells with effective antioxidant systems like glutathione. Current anticancer therapies focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger mechanisms to circumvent the oncogenic stress and to escape cell death. In this context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell protective mechanisms to confront the proteotoxicity of damaged and unfolded proteins. Proteotoxic stress is increased in tumor cells, thus providing an explanation for the anticancer selectivity of PES. In addition, we have found that PES induces a severe oxidative stress and the activation of p53. The reduction of the cell content in glutathione by means of L-buthionine-sulfoximine (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a central element in a series of positive feed-back loops in the cell. ROS, p53, proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the mechanisms leading to cell death, either apoptotic or necrotic. This network of interactions provides multiple targets for drug discovery and development in cancer.

Cite this article as:

Judit Ribas, Paolo Mattiolo and Jacint Boix , Pharmacological Modulation of Reactive Oxygen Species in Cancer Treatment, Current Drug Targets 2015; 16 (1) . https://dx.doi.org/10.2174/1389450115666141114153536