Targeting catalase in cancer
Christophe Glorieux, Pedro Buc Calderón
Abstract
Healthy cells have developed a sophisticated network of antioxidant molecules to prevent the toxic accumulation of reactive oxygen species (ROS) generated by diverse environmental stresses. On the opposite, cancer cells often exhibit high levels of ROS and an altered levels of antioxidant molecules compared to normal cells. Among them, the antioxidant enzyme catalase plays an essential role in cell defense against oxidative stress through the dismutation of hydrogen peroxide into water and molecular oxygen, and its expression is often decreased in cancer cells. The elevation of ROS in cancer cells provides them proliferative advantages, and leads to metabolic reprogramming, immune escape and metastasis. In this context, catalase is of critical importance to control these cellular processes in cancer through various mechanisms. In this review, we will discuss the major progresses and challenges in understanding the role of catalase in cancer for this last decade. This review also aims to provide important updates regarding the regulation of catalase expression, subcellular localization and discuss about the potential role of microbial catalases in tumor environment. Finally, we will describe the different catalase-based therapies and address the advantages, disadvantages, and limitations associated with modulating catalase therapeutically in cancer treatment. • RARα and JunB control catalase gene transcription in cancer cells. • The catalase subcellular localization is not restricted to peroxisomes. • Decreased catalase expression induces tumor proliferation and angiogenesis. • Catalase deficiency influences tumor metabolism, immunity, and promotes metastasis. • Catalase-based therapy has shown promising antitumor effects in preclinical studies.