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

Clin Biochem. 2007 Feb;40(3-4):268-73. doi: 10.1016/j.clinbiochem.2006.09.012. Epub 2006 Oct 19.

Abstract

Objectives: To examine the effect of 17beta-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 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism*
  • Apoptosis / drug effects
  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Estrogen Receptor alpha / analysis
  • Estrogen Receptor beta / analysis
  • Female
  • Flavonoids
  • Humans
  • Isoenzymes / analysis
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Propiophenones / pharmacology*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism

Substances

  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Flavonoids
  • Isoenzymes
  • Propiophenones
  • RNA, Messenger
  • Estradiol
  • Alkaline Phosphatase
  • xanthohumol