Le Gal · Science translational medicine 2015 · preclinical animal and in vitro mechanistic study · n=?

Antioxidants can increase melanoma metastasis in mice.

Cited 628 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Preclinical animal model and in vitro cell culture study

PubMed 26446958 · doi:10.1126/scitranslmed.aad3740 · record verified 2026-08-30

What was done

Researchers evaluated the effect of N-acetylcysteine (NAC) on tumor growth and lymph node metastasis using an endogenous mouse model of malignant melanoma. They also assessed the effects of NAC and the vitamin E analog Trolox on the proliferation, migration, and invasion of human malignant melanoma cell lines in vitro, and investigated underlying mechanisms involving glutathione oxidation ratios and RHOA GTPase signaling.

What was found

NAC administration increased lymph node metastases in mice but had no impact on the number or size of primary tumors. In human melanoma cell cultures, both NAC and Trolox markedly increased migration and invasive properties without altering proliferation. The abstract reports no numerical values, hazard ratios, or sample sizes. Both antioxidants increased the ratio of reduced to oxidized glutathione in melanoma cells and lymph node metastases, and blocking downstream RHOA signaling abolished the antioxidant-induced cell migration.

Why it matters

These findings suggest that antioxidant supplementation could paradoxically accelerate metastatic spread in melanoma rather than prevent cancer progression, highlighting potential risks of antioxidant use in cancer patients.

Limits

The findings are derived entirely from animal models and in vitro human cell lines; direct clinical effects and outcomes in human patients were not studied. The abstract provides no sample sizes, specific drug dosages, or quantitative effect sizes.

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