gms | German Medical Science

Objective: Interfering with the estrogen receptor alpha pathway appears an attractive way to eliminate tumor cells in pituitary adenomas. Here we attempted to assess the potency of several anti-estrogens on cell viability in rodent pituitary adenoma cells.

Methods: TtT-GF and GH3 cells were incubated with Bazedoxifene, Clomiphen, Fulvestrant, Raloxifene, and Tamoxifen in a submicromolar to high micromolar concentration range for up to five days. Cell viability was assessed using either a water soluble tetrazolium (WST)-1 assay or 4',6-diamidino-2-phenylindole (DAPI) staining. Half-maximal inhibitory concentrations (IC₅₀) of anti-estrogens were calculated based on three independent experiments performed in triplicates.

Results: After five days, viability of TtT-GF cells was significantly decreased by Bazedoxifene (IC₅₀=35µM, p=0.0044), Clomiphen (IC₅₀=5µM, p<0.0001), and Raloxifene (IC₅₀=20µM, p=0.013), while Fulvestrant did not show a significant effect on TtT-GF cell viability even at high micromolar concentrations. Similarly, after five days, viability of GH3 cells was significantly decreased by Bazedoxifene (IC₅₀=20µM, p=0.013), Clomiphen (IC₅₀=15µM, p=0038), Fulvestrant (IC₅₀=1µM, p<0.022), and Raloxifene (IC₅₀=35µM, p=0.031).

Conclusion: Viability of TtT-GF and GH3 cells was selectively decreased by anti-estrogens, of which Clomiphen had the highest potency in both cell lines. Further investigation of anti-estrogens in human cell lines is warranted to evaluate the clinical potential of anti-estrogens in pituitary adenomas.