Figure 5.
Inhibition of γ-Secretase has antineoplastic effects on breast cancer cell lines and affects cyclins A and B1 as well as NOXA. A, dose-response curve of growth inhibition by GSI alone in T47D:A18 breast cancer cells. B, dose response of 4-OH-TAM in the same cells in the absence of GSI and in the presence of two sub-IC50 concentrations of GSI. Growth inhibition assays showed that 4-OH-TAM at a concentration as low as 0.8 μmol/L caused significant growth inhibition in T47D:A18 cells in the presence of 0.2 and 0.4 μmol/L of GSI (IC50 of GSI alone, 0.84 μmol/L). The IC50 of 4-OH-TAM alone in this assay is 11 μmol/L. C, Western blots of MDA-MB231 cells treated for 24 h with GSI (1 μmol/L). This treatment decreased cyclins A and B1 and induced NOXA. D, Western blots of T47D:A18 cells treated for 48 h, showing that 0.4 μmol/L GSI alone, 10 μmol/L 4-OH-TAM alone, or a combination inhibited expression of cyclins A and B1. Only the combination caused induction of NOXA at 24 h.