Glutathione-S-transferase enhances proliferation-migration and protects against shikonin-induced cell death in breast cancer cells

AbstractGlutathione-S-transferase (GST) is a cytoplasmic protein responsible for detoxification, but the effect of the enzyme on cell biological events, including proliferation and migration, has never been reported. Thus, we evaluated the detoxification effect of in vitro–applied GST on cancer cell proliferation and migration. Assays for proliferation and migration of human breast cancer cells in the presence of GST were carried out. Binding of GST on the surface of the cancer cells was studied by flow cytometry. Detoxification through GST pathway was studied in the presence of shikonin. The effective dosage of GST in enhancement of cell proliferation was 10–50nM, and the cell migration could be significantly enhanced after 6 hours in the presence of 2–50nM GST. Therefore, overall cell proliferation and migration could be enhanced in the presence of 10nM or greater concentration of GST, and 15μM shikonin-induced toxification of the cancer cells could be neutralized by 1.0μM GST. Flow cytometry showed that GST directly bound to the surface of the cancer cells, and this was confirmed by fluorescence confocal microscopic observation. It is concluded that human class π-GST enhances proliferation and migration of human breast cancer cells by means of direct binding to the cell surface and maintaining cell viability by detoxification