Comparison of the Effect of Selenite on Drug-Resistant and -Sensitive Tumor Cells
The development of tumor cell drug resistance is considered a major cause for the failure of cancer therapy. In many cases drug resistant tumor cells have been shown to contain high levels of glutathione (GSH). Selenium compounds are known to act as anti-cancer agents and compounds such as selenite have been shown to induce cytotoxic effects in tumor cells. The available evidence suggests that for selenite, in contrast to most xenobiotics, a high level of intracellular GSH is correlated with a high degree of cytotoxicity. Based upon these observations, we hypothesized that tumor cells with high GSH levels, which are resistant to chemotherapeutic agents, will prove to be extremely sensitive to selenite. We examined this hypothesis in vitro by comparing the effects of selenite on drug resistant human ovarian tumor (NIH:OVCAR-3) cells, which have high GSH levels, and non-resistant human ovarian tumor (A2780) cells with low GSH levels. We employed three assays which measure different aspects of cytotoxicity in vitro: cell viability (ability of cells to exclude trypan blue), proliferation of viable cells, and attachment of cells to a solid matrix. In each of these assays the drug resistant cells proved to be significantly more sensitive to selenite than the drug sensitive cells. This study represents the first step in the evaluation of selenite as a treatment for drug-resistant tumors.