Clinical trials of antioxidants in cancer have yielded inconsistent results. In a study reported in Science Translational Medicine, Sayin and colleagues evaluated the effects of the antioxidants N-acetylcysteine and vitamin E in mouse models of BRAF- and KRAS-induced lung cancer. N-acetylcysteine and vitamin E dietary supplementation markedly increased tumor progression and reduced survival in the mouse models.
RNA sequencing showed that the structurally unrelated compounds resulted in highly coordinated changes in tumor transcriptome profiles, predominantly featuring reduced expression of endogenous antioxidant genes. Both N-acetylcysteine and vitamin E increased tumor cell proliferation by reducing reactive oxygen species (ROS), DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 resulted in tumor growth similar to that observed with antioxidant supplementation while eliminating the antioxidant effect, indicating that antioxidants accelerate tumor growth by disrupting the ROS-p53 axis.
The investigators noted, “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 [N-acetylcysteine] to relieve mucus production.” ■