Can Antioxidants Increase Cancer cells Metastasis

Can Antioxidants Increase Cancer cells Metastasis ?

Two recent studies published in Journal Nature (Oct 4, 2015) and Science Translational Medicine (Oct 7, 2015) reported the above findings in mice.

According to article published in Science Transl Med (Oct 7, 2015) by Kristell Le Gal et al (Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY):
* Administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors.
* NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation.
* Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis.
* Both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration.

These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression.

Link: http://stm.sciencemag.org/content/7/308/308re8.short

Similar findings were reported by Sean J. Morrison et al in journal nature (Oct 4 2015):
* Oxidative stress limits distant metastasis by melanoma cells in vivo.
* Treatment with the antioxidant NAC increased tumor formation by intravenously transplanted melanoma cells.

Link: http://www.nature.com/nature/journal/vaop/ncurrent/fig_tab/nature15726_ST3.html