Mitochondrial reactive oxygen species and cancer

Abstract

Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity. While initial studies focused on the damaging effects of reactive oxygen species, a recent paradigm shift has shown that mROS can act as signaling molecules to activate pro-growth responses. Cancer cells have long been observed to have increased production of ROS relative to normal cells, although the implications of this increase were not always clear. This is especially interesting considering cancer cells often also induce expression of antioxidant proteins. Here, we discuss how cancer-associated mutations and microenvironments can increase production of mROS, which can lead to activation of tumorigenic signaling and metabolic reprogramming. This tumorigenic signaling also increases expression of antioxidant proteins to balance the high production of ROS to maintain redox homeostasis. We also discuss how cancer-specific modifications to ROS and antioxidants may be targeted for therapy.

Effects of aging on the male reproductive system

“…These unpaired electrons make free radicals highly reactive towards carbohydrates, lipids, proteins, nucleic acids, and other cellular molecules [50,51]. Free radicals arise from normal cell metabolism or can be produced by exogenous sources including radiation, herbicides, cigarette smoking, chronic stress, alcohol abuse, some drugs, and air pollution [52,53].…”

Oxidative stress and breast cancer biomarkers: the case of the cytochrome P450 2E1

“…[2] Accumulating evidence indicates that apart from their harmful effects ROS act as second messenger signalling molecules regulating numerous pathways including cell cycle, [3] autophagy, [4,5] apoptosis, [6] endoplasmic reticulum (ER) stress [7] and cellular energy metabolism. [8,9] Sources of intracellular ROS generation include both organelles such as mitochondria, ER and peroxisomes as well as enzymes such as the NADPH oxidases, xanthine oxidase, lipoxygenases and cytochrome P450 enzymes, which produce ROS through their enzymatic activities. [10] CYP450 enzymes are mainly involved in the phase I metabolism of a wide range of exogenous and endogenous compounds oxidizing them to form more hydrophilic molecules thereby facilitating easier clearance.…”

Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

“…Among these, superoxide, hydrogen peroxide and hydroxyl radicals are the most potent and well studied species. The roles of reactive oxygen species in tumorigenesis , prevention, and therapy has been discussed in more recent reviews (Liou & Storz, 2010;Sullivan & Chandel, 2014;Haliwell, 2001;Kovacic & Jacintho, 2001a;Gupta, Hevia, Patchva, Park, Koh, & Aggarwal, 2012 A variety of enzymatic and non-enzymatic sources of ROS exists in the biological system. Enzymes within the cell are primary sources of ROS/RNS.…”

“…In recent years, a large body of literature has emerged documenting the link between ROS, reactive nitrogen species (RNS), OS and ET and cancer (Liou & Storz, 2010;Sullivan & Chandel, 2014;Haliwell, 2001). …”

“…Heavy metals, like Hg, Pb, Cd, Cr, and Cu, metal complexes, nano particles, cigarette smoke, pollutants from automobiles, fossil burning furnaces, various drugs and certain types of other chemical compounds (Scheme 1) play a role. In cancer affected cells, high levels of ROS can result from mitochondrial dysfunction, high metabolic activity, cellular signaling, peroxisome activity, oncogene activity, oxidase activity, cyclooxygenase and lipoxigenase activity (Liou & Storz, 2010;Sullivan & Chandel, 2014;Haliwell, 2001). …”