Abstract

Reactive oxygen species (ROS) result from intracellular aerobic metabolism and/or extracellular stimuli. Although endogenous antioxidant systems exquisitely balance ROS production, an excess of ROS production, commonly found in diverse human degenerative pathologies including cancer, gives rise to the oxidative stress. Increased oxidative stress in cancer is related to the sustained proliferation and metabolism of cancer cells. However, cancer cells show an intrinsic higher antioxidant capacity with respect to the normal counterpart as well as an ability to cope with oxidative stress-induced cell death by establishing mechanisms of adaptation, which define a selective advantage against the adverse oxidative stress environment. The identification of survival factors and adaptive pathways, set up by cancer cells against oxidative stress, provides multiple targets for the therapeutic intervention against cancer. Neuroglobin (NGB), a globin primarily described in neurons as an oxidative stress sensor and cytoprotective factor against redox imbalance, has been recently recognized as a novel tumor-associated protein. In this review, the involvement of NGB in the cancer cell adaptation and resistance to oxidative stress will be discussed highlighting the globin role in the regulation of both the stress-induced apoptotic pathway and antioxidant systems activated by cancer cells.

Highlights

  • Reactive oxygen species (ROS), including superoxide anion ((OOH2-)⋅), hydrogen peroxide (H2O2), and are abundant products of aerobic hydroxyl radical metabolism, and their levels set up the intracellular redox state [1]

  • Among different proteins that could serve as a compensatory element, here, we discuss the role of Neuroglobin (NGB), a monomeric heme-protein that operates as an oxidative stress biosensor and player in the context of the compensatory/adaptive systems of cancer cells

  • We demonstrated that oxidative stress mainly increases NGB levels by acting, like E2, through the inhibition of lysosomal protein degradation and the increase of the protein translation rate [66]

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Summary

Introduction

Reactive oxygen species (ROS), including superoxide anion ((OOH2-)⋅), , hydrogen peroxide (H2O2), and are abundant products of aerobic hydroxyl radical metabolism, and their levels set up the intracellular redox state [1]. The exact mechanism is still unclear, ROS represent the main selective pressure, which could induce cancer cell death or activate aberrant adaptation mechanisms involved in the acquisition of almost all the cancer hallmarks, including sustained cell proliferation, immortalization, cell death escape, metastasis, and chemo resistance [3]. These two faces played by ROS in cancer have been translated into two different strategies to develop anticancer agents. Among different proteins that could serve as a compensatory element, here, we discuss the role of Neuroglobin (NGB), a monomeric heme-protein that operates as an oxidative stress biosensor and player in the context of the compensatory/adaptive systems of cancer cells

Neuroglobin as a Stress Sensor in the Brain
Neuroglobin in Cancer
ER훼 PI3K AKT
Neuroglobin and Oxidative Stress Signaling in Cancer
Conclusion and Perspectives
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