Effect of Arsenite on Nitrosative Stress in Human Breast Cancer Cells and Its Modulation by Flavonoids

Abstract

Arsenic (As) is used in the treatment of leukemia and breast cancer due to its oxidative cytotoxic action. However, it is also toxic to normal cells. One proposed anticancer mechanism induced by As might be nitrosative stress (NS). It is believed that antioxidant flavonoids in combination with As might reduce its toxic action on normal cells without interfering with its antitumor action. In the present study, we evaluated the antineoplastic potential of As on breast human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids, such as quercetin (Q) and silymarin (S). Even though both cell lines differed about their oxidative responsiveness, their viability was decreased by NS induction through γ-glutamyltranspeptidase inhibition. Arsenic triggered NS in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without recovering their pre-treatment capacity. ZR-75-1 cells maintained their antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not. Silymarin did not interfere with the described As bioactivity. NS was an anticancer mechanism exerted by As depending on the redox cellular response that could be differentially modified by dietary antioxidants. Hence, it is worthwhile to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy, especially when using As.