Distinct modulation of alkaline phosphatase isoenzymes by 17β-estradiol and xanthohumol in breast cancer MCF-7 cells

Objectives: To examine the effect of 17β-estradiol and xanthohumol in alkaline phosphatase (ALP) expression and activity in breast cancer MCF-7 cells. Design and methods: ALP isoenzymes expression was evaluated by RT-PCR and Western blotting. ALP activity was measured by spectrophotometry. Cell proliferation and apoptosis were examined by MTT and immunostaining for KI67 and TUNEL, respectively. Results: ALP isoenzymes expression and activity were decreased by 1 nM 17β-estradiol. Pure estrogenic antagonist (ICI 182,780) reversed 17β-estradiol-inhibiting effect in TNS-ALP expression. RNA and protein expression of IALP, but not TNS-ALP, was also decreased by incubation with 10 μM xanthohumol (IC50) and was accompanied by a significant reduction in ALP activity. Treatment with 17β-estradiol enhanced cell proliferation and decreased apoptosis. Conversely, xanthohumol incubation inhibited cell viability and apoptosis. Conclusion: Estrogens and xanthohumol differently modulate ALP isoenzymes. ALP loss associated with increased cell proliferation. Modulation of this enzyme by 17β-estradiol and xanthohumol might provide therapeutic strategies against hormone-dependent breast cancer.