Tea polyphenols modulate antioxidant redox system on cisplatin-induced reactive oxygen species generation in a human breast cancer cell

Abstract

Tea polyphenols (TPP) have potent antioxidant and anticancer properties, particularly in patients undergoing radiation or chemotherapy. However, few studies have been conducted on treatments using a combination of TPP and the conventional chemical anticancer drug cisplatin (CP). This study was designed to investigate the mechanism of the cytotoxicity of total TPP and CP, which may synergistically induce cell death in cancer cells. Here, breast cancer cells (MCF-7) were treated with various concentrations of TPP alone or in combination with the chemotherapeutic drug CP. The effect of TPP on cell growth, intracellular reactive oxygen species (ROS) level, apoptosis and gene expression of caspase-3, caspase-8 and caspase-9 and p53 was investigated. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that the MCF-7 cells were less sensitive to growth inhibition by TPP treatment than either CP or the combination therapy. Propidium iodide nuclear staining indicated that exposure to this combination increased the proportion of apoptotic nuclei compared with a single-agent treatment. Flow cytometry analysis was used to quantify changes in intracellular ROS. Detection of activated caspases by fluorescently labelled inhibitors of caspases (FLICA) combined with the plasma membrane permeability assay demonstrated that the percentage of early and late apoptotic/secondary necrotic cells was higher in the cells treated with the combination than in those treated with either TPP or CP alone. The combined TPP and CP treatment synergistically induced apoptosis through both caspase-8 and caspase-9 activation and p53 over-expression. This suggests that TPP plus CP may be used as an efficient antioxidant-based combination therapy for estrogen receptor (ER)-positive and p53-positive breast cancer.