Pharmacological Modulation of Reactive Oxygen Species in Cancer Treatment

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

Journal Name: Current Drug Targets

Volume 16 , Issue 1 , 2015

  Journal Home
Translate in Chinese
Submit Manuscript
Submit Proposal

Abstract:

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.

Keywords: Cell death, Cell experimental pharmacology, L-buthionine-sulfoximine, Mdivi-1, Oxidative stress, p53, 2- phenylethinesulfoxamine, proteotoxic stress.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 1
Year: 2015
Page: [31 - 37]
Pages: 7
DOI: 10.2174/1389450115666141114153536

Article Metrics

PDF: 61
HTML: 3
EPUB: 1
PRC: 1