Suppression of cell proliferation by inhibition of estrone-3-sulfate transporter in estrogen-dependent breast cancer cells

Pharm Res. 2005 Oct;22(10):1634-41. doi: 10.1007/s11095-005-7096-0. Epub 2005 Sep 22.


Purpose: The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells.

Methods: The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells was measured, and inhibitory study using various organic anions on estrone-3-sulfate uptake by MCF-7 cells was conducted. The effects of the inhibitor on the transcription of reporter gene and cell proliferation induced by estrone-3-sulfate were examined.

Results: The uptake of estrone-3-sulfate by MCF-7 cells was saturable with Km value of 2.32 microM. The uptake was Na+-independent and was inhibited by several anionic compounds such as bromosulfophthalein. Bromosulfophthalein also significantly inhibited the transcription of reporter gene via estrogen response element and cell proliferation induced by estrone-3-sulfate. However, the transcriptional activation or cell proliferation induced by estrone was not inhibited by bromosulfophthalein. Reverse transcription-polymerase chain reaction analysis revealed the expression of mRNA of organic anion transporting polypeptide (OATP)-D and OATP-E as possible candidates to transport estrone-3-sulfate.

Conclusions: The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.

MeSH terms

  • Alkaline Phosphatase / biosynthesis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Estrogens / pharmacology*
  • Estrone / analogs & derivatives*
  • Estrone / antagonists & inhibitors
  • Estrone / pharmacokinetics
  • Female
  • Humans
  • Indicators and Reagents / pharmacology
  • Membrane Transport Proteins / drug effects*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Sulfobromophthalein / pharmacology
  • Transcriptional Activation


  • Estrogens
  • Indicators and Reagents
  • Membrane Transport Proteins
  • Sulfobromophthalein
  • Estrone
  • Alkaline Phosphatase
  • estrone sulfate