Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells

Breast Cancer Res Treat. 2002 Jan;71(1):37-45. doi: 10.1023/a:1013301408464.

Abstract

We have previously demonstrated that the pineal hormone, melatonin, can inhibit the growth of estrogen receptor-alpha (ERalpha)-positive breast cancer cells and suppress ERalpha gene transcription. To investigate the relationship between the estrogen response pathway and melatonin's growth inhibition, ERalpha-positive MCF-7 human breast cancer cells were transiently transfected with an estrogen response element (ERE) luciferase reporter construct and then treated with melatonin (10(-9)-10(-6) M) for 30 min followed by 10(-9) M 17-beta-estradiol (E2) or treated with each compound alone. Melatonin pre-treatment significantly reduced E2-induced ERalpha transactivation and ERalpha-ERE binding activity. We also conducted experiments to determine if melatonin modulates cAMP levels in MCF-7 cells. Melatonin inhibited the forskolin-induced and E2-induced elevation of cAMP levels by 57 and 45%, respectively. These data indicate that melatonin can act as a biological modifier to affect ERalpha transcriptional activity by regulating signal transduction pathways which impinge on the ERalpha and by altering E2-mediated ERalpha transactivation and ERalpha DNA binding activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Breast Neoplasms / pathology*
  • Cyclic AMP / biosynthesis*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melatonin / pharmacology*
  • Receptors, Estrogen / biosynthesis*
  • Signal Transduction
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Adjuvants, Immunologic
  • Estrogen Receptor alpha
  • Receptors, Estrogen
  • Estradiol
  • Cyclic AMP
  • Melatonin