Oxidative stress induced lung cancer and COPD: opportunities for epigenetic therapy.
Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings.
Lawless
Matthew W
MW
Centre for Liver Disease, School of Medicine and Medical Science, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
O'Byrne
Kenneth J
KJ
Gray
Steven G
SG
D000818:Animals; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D056572:Histone Deacetylase Inhibitors