Free radicals, metals and antioxidants in oxidative stress-induced cancer

Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants.

Free Radical Lipid Peroxidation: Mechanisms and Analysis

The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research.

Ferroptosis: mechanisms, biology and role in disease.

The primary producs formed from the autoxidation of lipids can be understood based upon a mechanism that involves five different reaction types. These reactions are: reaction of a carbon radical and molecular oxygen, atom transfer of a hydrogen from substrate to the chain carrying peroxyl, fragmentation of the chain carrying peroxyl to give oxygen and a carbon radical, rearrangement of the peroxyl, and cyclization of the peroxyl. The mechanisms of these primary reaction steps has been the focus of extensive research over the past fifty years, and the current level of understanding of these transformations is the subject of this review.

Mechanisms of free radical oxidation of unsaturated lipids

The mechanism of the 3,2 allylperoxyl rearrangement : a radical-dioxygen pair reaction that proceeds with stereochemical memory

An allyl radical-dioxygen caged pair mechanism for cis-allylperoxyl rearrangements

Reaction of O-tertiary alkyl arylhydroxamate esters with nitrosyl chloride gives O-tertiary alkyl aryl peresters that can be hydrolyzed to the hydroperoxide. If the hydroxamate ester carbonyl oxyge...

Sarah E. Caldwell

Papers

Mechanisms of free radical oxidation of unsaturated lipids

The mechanism of the 3,2 allylperoxyl rearrangement : a radical-dioxygen pair reaction that proceeds with stereochemical memory

An allyl radical-dioxygen caged pair mechanism for cis-allylperoxyl rearrangements

Preparation of Unsymmetrically Labeled Hydroperoxides. A Hydroxamate Ester−Nitrosation Approach

Preparation and Reactions of Unsymmetrically Labeled Hydroperoxides: Solvent Viscosity Dependent Oxygen Scrambling of Cumylperoxyl Free Radicals