Transcriptomics

Dataset Information

301

Antioxidants Accelerate Lung Cancer Progression in Mice


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. Here, 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 inactivating the ROS-p53 axis. Because p53 inactivation occurs 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. There were 3 experimental groups (untreated, NAC-treated and Vitamin E-treated. Each group consisted of 5 animals, and from each animal we harvested 2 tumor samples. Hence, in total 3x10=30 samples were profiled.

ORGANISM(S): Mus musculus  

SUBMITTER: Jonas A Nilsson   Volkan I Sayin  Mohammed X Ibrahim  Per Lindahl  Martin O Bergo  Erik Larsson 

PROVIDER: E-GEOD-52594 | ArrayExpress | 2014-01-31

SECONDARY ACCESSION(S): SRP033220GSE52594PRJNA229429

REPOSITORIES: GEO, ArrayExpress, ENA

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Antioxidants accelerate lung cancer progression in mice.

Sayin Volkan I VI   Ibrahim Mohamed X MX   Larsson Erik E   Nilsson Jonas A JA   Lindahl Per P   Bergo Martin O MO  

Science translational medicine 20140101 221


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 mou  ...[more]

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