Identification of cadmium-produced lipid hydroperoxides, transcriptomic changes in antioxidant enzymes, xenobiotic transporters, and pro-inflammatory markers in human breast cancer cells (MCF7) and protection with fat-soluble vitamins.

Cadmium (Cd) is a toxic metal that is regarded as a metallohormone with estrogen-like properties. The present study aimed at identification of lipid hydroperoxides produced in human breast cancer (MCF7) exposed to cadmium (Cd) at environmentally relevant levels. Cd induced cytotoxicity and oxidative stress and produced a series of 26 lipid hydroperoxide species including 14 phosphatidylcholine hydroperoxides (PC-OOH), 9 triacylglycerol hydroperoxides (TG-OOH), and 3 cholesteryl ester hydroperoxides (CE-OOH). Among these hydroperoxides, PC34:2-OOH, PC34:3-OOH, TG60:14-OOH, TG48:5-OOH, TG60:15-OOH, and CE20:4-OOH were produced in a dose-dependent manner, suggesting these as possible biomarkers for Cd exposure in MCF7 cells. In addition, Cd led to significant decreases in the gene expressions of antioxidants, detoxification enzymes, and xenobiotic transporters. In a protection trial, co-exposure of MCF7 cells to fat-soluble vitamins including vitamin A, D, and E reduced Cd-induced cytotoxicity, lipid peroxidation, oxidative stress, and inflammatory responses. Fat-soluble vitamins upregulated antioxidant and detoxification enzymes, and xenobiotic transporters. Therefore, dietary supplementation of such micronutrients is recommended for people at risk for exposure to Cd.