Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy

TLDR

Reactive oxygen species and lipid peroxidation, producing 4‑hydroxynonenal, are common in cancer cells and can trigger apoptosis, yet tumor cells may adapt to oxidative stress and develop drug resistance. The paper reviews recent advances linking oxidative stress and lipid peroxidation products to cancer progression, emphasizing pro‑oxidant anticancer agents and drug‑resistance mechanisms that could be targeted to improve therapy. It surveys studies on how oxidative stress and lipid peroxidation influence cancer biology, focusing on the role of pro‑oxidant agents and resistance pathways that can be modulated for better therapeutic outcomes.

Abstract

The generation of reactive oxygen species (ROS) and an altered redox status are common biochemical aspects in cancer cells. ROS can react with the polyunsaturated fatty acids of lipid membranes and induce lipid peroxidation. The end products of lipid peroxidation, 4-hydroxynonenal (HNE), have been considered to be a second messenger of oxidative stress. Beyond ROS involvement in carcinogenesis, increased ROS level can inhibit tumor cell growth. Indeed, in tumors in advanced stages, a further increase of oxidative stress, such as that occurs when using several anticancer drugs and radiation therapy, can overcome the antioxidant defenses of cancer cells and drive them to apoptosis. High concentrations of HNE can also induce apoptosis in cancer cells. However, some cells escape the apoptosis induced by chemical or radiation therapy through the adaptation to intrinsic oxidative stress which confers drug resistance. This paper is focused on recent advances in the studies of the relation between oxidative stress, lipid peroxidation products, and cancer progression with particular attention to the pro-oxidant anticancer agents and the drug-resistant mechanisms, which could be modulated to obtain a better response to cancer therapy.