Antioxidants Cause Melanoma to Metastasize Faster

A new study suggests that antioxidant use can double the rate of melanoma metastasis in mice, reinforcing findings that indicate they can hasten the progression of lung cancer.

Researchers at Sahlgrenska Academy (Göteborg, Sweden) and the University of Gothenburg (Sweden) conducted a study in a murine model to examine the impact of using N-acetylcysteine (NAC, an antioxidant that is a specially modified form of the dietary amino acid cysteine), and the soluble vitamin E analog Trolox on progression of malignant melanoma. The study was launched following previous trials that showed that antioxidants actually increase cancer risk, and could even accelerate the progression of primary lung tumors.

The results showed that NAC increases lymph node metastases, but has no impact on number and size of primary tumors. Similarly, NAC and Trolox increase the migration and invasive properties of human malignant melanoma cells, but do not affect proliferation. Both increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, with increased migration dependent on new glutathione synthesis. NAC and Trolox also increase activation of the small guanosine triphosphatase RHOA; blocking downstream RHOA signaling abolished antioxidant-induced migration. The study was published on October 7, 2015, in Science Translational Medicine.

“Taking nutritional supplements containing antioxidants may unintentionally hasten the progression of a small tumor or premalignant lesion, neither of which is possible to detect,” said senior author Prof. Martin Bergö, PhD, of the Sahlgrenska Academy. “Our current research combined with information from large clinical trials with antioxidants suggests that people who have been recently diagnosed with cancer should avoid such supplements."

Oxidation is a chemical reaction involving the loss of electrons or an increase in oxidation state, a process that can produce free radicals. As well-established, long term evidence shows that free radicals can cause cancer, many researchers thought that antioxidants, which destroy free radicals, could provide protection against the disease. Accordingly, antioxidants are found in many nutritional supplements, touted as a means of preventing cancer. Antioxidant use is particularly relevant in melanoma, not only because melanoma cells are known to be sensitive to free radicals, but because the cells can be exposed to antioxidants by non-dietary means as well.

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Sahlgrenska Academy
University of Gothenburg