RT Journal Article
SR Electronic
T1 Antioxidants Accelerate Lung Cancer Progression in Mice
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 221ra15
OP 221ra15
DO 10.1126/scitranslmed.3007653
VO 6
IS 221
A1 Sayin, Volkan I.
A1 Ibrahim, Mohamed X.
A1 Larsson, Erik
A1 Nilsson, Jonas A.
A1 Lindahl, Per
A1 Bergo, Martin O.
YR 2014
UL http://stm.sciencemag.org/content/6/221/221ra15.abstract
AB 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.