Le Gal et al (Sci Transl Med. 2015;7:308re8) discovered that antioxidant administration in mice not only increased lymph node metastases but also increased the migration and invasive properties of human melanoma cells. However, the antioxidant N-acetylcysteine (NAC) had no impact on the number and size of the primary tumors (in mice), and neither NAC nor Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a structurally unrelated antioxidant and soluble vitamin E analogue, affected the proliferation of human melanoma cells. Hence, the progression of malignant melanoma (MM), a cancer that is sensitive to changes in reduction-oxidation status, may be influenced by exposure to antioxidants and vitamin E.
What’s the issue?
Healthy individuals and oncology patients commonly use supplements containing antioxidants to prevent cancer and fight malignancy, respectively. However, animal studies and human clinical trials have shown that antioxidants increase cancer risk and accelerate the progression of primary lung tumors. Le Gal et al’s study regarding progression of melanoma metastases following exposure to antioxidants extends the observations demonstrated for lung neoplasms. N-acetylcysteine was added to the drinking water of mice, whereas NAC and Trolox were added to a panel of human MM cell lines. N-acetylcysteine increased lymph node metastases in the endogenous mouse model of MM, and both NAC and Trolox markedly increased the migrations and invasive properties of human MM cells.
Cancers may be caused or exacerbated by free radicals. It has been assumed that antioxidants may protect against malignancy by destroying free radicals. Although prior studies have concluded that antioxidants prevent healthy cells from transforming into cancer after exposure to free radicals, Le Gal et al’s research suggests that antioxidants may not only protect but also enhance tumor progression once a cancer has developed.
If one extends the results of animal and tissue culture studies to humans, exposure to antioxidants may potentially influence the course of metastatic disease in patients who have already developed melanoma. In addition to systemic exposure after receiving oral antioxidants, melanoma patients also can be topically exposed to antioxidants. For example, nonprescription skin care products such as cutaneous rejuvenation treatments, emollients, and sunscreens can contain β-carotene, vitamin E, and other antioxidants. It remains to be determined whether topical exposure to antioxidants can cause the same observations that have occurred following systemic absorption in mice or tissue culture studies in human cell lines. Should we caution our melanoma patients with regards to what they apply to their skin?