When Oxidative Stress Meets Epigenetics: Implications in Cancer Development

Abstract

Cancer is one of the leading causes of death worldwide and it can affect any part of the organism. It arises as a consequence of the genetic and epigenetic changes that lead to the uncontrolled growth of the cells. The epigenetic machinery can regulate gene expression without altering the DNA sequence, and it comprises methylation of the DNA, histones modifications, and non-coding RNAs. Alterations of these gene-expression regulatory elements can be produced by an imbalance of the intracellular environment, such as the one derived by oxidative stress, to promote cancer development, progression, and resistance to chemotherapeutic treatments. Here we review the current literature on the effect of oxidative stress in the epigenetic machinery, especially over the largely unknown ncRNAs and its consequences toward cancer development and progression.

Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia

“…In this way, redox sensors rapidly respond to changes in ROS levels and activate pathways leading either to cell death or to survival and adaptation to elevated ROS levels. The list of redox signaling proteins is continuously growing and comprises small GTPases, kinases including mammalian target of rapamycin (mTOR), MAP and AKT kinases, and phosphatases such as the family of protein tyrosin phosphatases (PTPs) as well as transcriptional factors and epigenetic modulators that are involved in complex cross-talk networks as recently reported [ 87 , 88 ].…”

Ameliorative Effects of the Sesquiterpenoid Valerenic Acid on Oxidative Stress Induced in HepG2 Cells after Exposure to the Fungicide Benomyl

“…HO and nuclear factor-kappa B (NF-κB) act as cell protectors against stress. Another cellular protection mechanism against stress is the activation of heat shock proteins (HSP) (e.g., hsp70 and hsp 90) [ 45 , 46 , 47 , 48 ]. During excessive cellular oxidative stress conditions, cells increase their antioxidant capacity via triggering the Nrf2/HO-1 pathway.…”

“…This process results in downregulation of the inflammatory process, and additionally, Nrf2/HO-1 pathway activation induces an increase in anti-inflammatory cytokine action. Another important function of Nrf2 is regulating GSH synthesis enzymes such as GST, GPx, and glutathione reductase [ 48 , 49 , 50 ]. Natural compounds, such as nutrition constituents or nutraceuticals, have diverse effects on the Nrf2/KEAP-1/HO-1 pathway, although the mechanisms have not been described yet [ 51 ].…”

Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank

“…The GI tract is highly exposed to reactive oxygen species (ROS) from external and internal sources, such as from cigarette smoke, alcohol consumption, viral/bacterial infections, or inflammatory disorders [ 2 ]. An imbalance between ROS and antioxidants can lead to oxidative-stress-induced damage to DNA, which is one of the major pathways that can lead to cancer development [ 3 ].…”