Distinct modulation of alkaline phosphatase isoenzymes by 17beta-estradiol and xanthohumol in breast cancer MCF-7 cells.
OBJECTIVE
To examine the effect of 17beta-estradiol and xanthohumol in alkaline phosphatase (ALP) expression and activity in breast cancer MCF-7 cells.


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 17beta-estradiol. Pure estrogenic antagonist (ICI 182,780) reversed 17beta-estradiol-inhibiting effect in TNS-ALP expression. RNA and protein expression of IALP, but not TNS-ALP, was also decreased by incubation with 10 microM xanthohumol (IC(50)) and was accompanied by a significant reduction in ALP activity. Treatment with 17beta-estradiol enhanced cell proliferation and decreased apoptosis. Conversely, xanthohumol incubation inhibited cell viability and apoptosis.


CONCLUSIONS
Estrogens and xanthohumol differently modulate ALP isoenzymes. ALP loss associated with increased cell proliferation. Modulation of this enzyme by 17beta-estradiol and xanthohumol might provide therapeutic strategies against hormone-dependent breast cancer.
Guerreiro
Susana
S
Department of Biochemistry, Faculty of Medicine of the University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Monteiro
Rosário
R
Martins
Maria João
MJ
Calhau
Conceição
C
Azevedo
Isabel
I
Soares
Raquel
R
D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D005260:Female; D005419:Flavonoids; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011427:Propiophenones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005419:Flavonoids; D007527:Isoenzymes; D011427:Propiophenones; D012333:RNA, Messenger; D004958:Estradiol; D000469:Alkaline Phosphatase; C104536:xanthohumol