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Antioxidants accelerate lung cancer progression in mice.

Journal article
Authors Volkan I. Sayin
Mohamed X Ibrahim
Erik Larsson
Jonas A Nilsson
Per Lindahl
Martin Bergö
Published in Science translational medicine
Volume 6
Issue 221
Pages 221ra15
ISSN 1946-6242
Publication year 2014
Published at Wallenberg Laboratory
Institute of Clinical Sciences, Department of Surgery
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 221ra15
Language en
Links dx.doi.org/10.1126/scitranslmed.300...
Subject categories Cancer and Oncology

Abstract

Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.

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