Ever since ROS (reactive oxygen species) were shown to meet the criteria of true signalling molecules, such as regulated production and a specific biological function, many efforts have been made to understand the precise role of ROS. The function of ROS in pathological mechanisms is taking a more and more central role in various fields of biomedical research, including neurobiology, cardiology and cancer. An elevated oxidative status has been found in many types of cancer cells, and the introduction of chemical and enzymological antioxidants can inhibit tumour cell proliferation, pointing to a critical role of ROS in mediating loss of growth control. The present review describes ROS-regulated mechanisms that are associated with cancer and tumour invasiveness. The cellular processes that are linked to these ROS functions are mitogenic signalling and cell motility, while ROS have also been implicated in apoptosis and cellular senescence, two mechanisms regarded as being anti-tumorigenic. This ‘two-faced’ character of free radicals will be discussed and placed in the context of the physiological conditions of the tumour cell, the different molecular backgrounds, and the specific ROS. More detailed understanding of the signalling pathways regulated by ROS in tumour cells will open up new prospects for chemo- or gene-therapeutic interventions.
- growth factor
- Mn superoxide dismutase
- reactive oxygen species (ROS)
679th Meeting of the Biochemical Society held at the University of Essex, Colchester, 2–4 July 2003
Abbreviations used: AP-1, activator protein-1; DPI, diphenylene iodonium; ERK, extracellular-signal-regulated kinase; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; PI3-K, phosphoinositide 3-kinase; ROS, reactive oxygen species; RTK, receptor tyrosine kinase; SOD, superoxide dismutase.
- © 2003 Biochemical Society