Antioxidants Accelerate Lung Cancer Progression in Mice

Science translational medicine (Impact Factor: 15.84). 01/2014; 6(221):221ra15. DOI: 10.1126/scitranslmed.3007653
Source: PubMed


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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Available from: Volkan I Sayin, Aug 25, 2014
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    • "On the other hand, the dietary polyphenol anti-oxidant epigallocatechin gallate (EGCG) demonstrated anticancer efficacy by itself in prostate cancer5455565758and the anti-oxidant tempol analog, OT-404, demonstrated effective anticancer efficacy and enhancement of chemotherapeutic response[59]. Past studies indicated that oral administration of anti-oxidants was either ineffective or even induced the proliferation and metastasis of various cancers[51,52,60,61]. However, these studies utilized only the oral administration route for the selected anti-oxidants, subjecting them to first-pass metabolism and a variety of other in vivo modifications via the digestive system. "
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    • "However, the increased micronuclei at both 30 and 45 days are internally consistent, and suggest that there may be a true NAC effect. These results might be related to the findings of Sayin et al. [39], showing that-in contrast to the general belief that antioxidants help fight cancer—treatment with the antioxidants NAC and vitamin E accelerated lung cancer progression in mice and increased tumor cell proliferation. It should be noted that a single relatively short (25 h) treatment with a high concentration of NAC was used in the present study. "
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    ABSTRACT: Increased level of micronuclei was observed in SH-SY5Y cells in a previous study at 8 and 15 days after exposure to extremely low frequency (ELF) magnetic fields (MF), indicating possible induction of genomic instability in the progeny of the exposed cells. The aim of this study was to further explore the induction of genomic instability by ELF MFs by increasing the follow-up time up to 45 days after exposure. Human SH-SY5Y neuroblastoma cells were exposed to a 50 Hz, 100 μT MF for 24 h with or without co-exposure to menadione (MQ), a chemical agent that increases cellular superoxide production. Micronuclei, reactive oxygen species (ROS) and lipid peroxidation (LPO) were measured at 15, 30 and 45 days after exposure. To study the possible causal role of ROS in the delayed effects of MF, the antioxidant N-acetylcysteine (NAC) was administered before MF exposure. Consistently with the previous study, the level of micronuclei was statistically significantly elevated 15 days after exposure. A similar effect was observed at 30 days, but not at 45 days after exposure. The level of LPO was statically significantly decreased 30 and 45 days after exposure. Consistently with our previous findings, the MF effect did not depend on co-exposure to MQ. Treatment with NAC effectively decreased cellular ROS level and suppressed the effect of MQ on ROS, but it did not block the MF effect, indicating that increase in ROS is not needed as a causal link between MF exposure and induction of delayed effects. The results presented here are consistent with genomic instability that persists in the progeny of MF-exposed cells up to at least 30 days after exposure. Changes in LPO observed at 30 and 45 days after exposure indicates that the MF-initiated process may continue up to at least 45 days after exposure.
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    • ", однак ці дані неоднозначні[8]. Слід зауважити, що надмірна ліпопероксидація є одним з механізмів реалізації як терапевтичних ефектів, так і побічних ефектів протипухлинних лікарських засобів, у тому числі мелфалану. "

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