Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer

T. J. Thomas, Thresia Thomas, Shali John, Hui Chen Hsu, Ping Ar Yang, Tuomo A. Keinänen, Mervi T. Hyvönen

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12 Scopus citations


Tamoxifen is the most widely used drug to treat women with estrogen receptor α (ERα)-positive breast cancer. Endoxifen is recognized as the active metabolite of tamoxifen in humans. We studied endoxifen effects on ERα-positive MCF-7 breast cancer cells. Estradiol increased the proliferation of MCF-7 cells by two- to threefold and endoxifen suppressed its effects. Endoxifen suppressed c-myc, c-fos and Tff1 oncogene expression, as revealed by RT-PCR. Estradiol increased the activity of ornithine decarboxylase (ODC) and adenosyl methioninedecarboxylase (AdoMetDC), whereas endoxifen suppressed these enzyme activities. Endoxifen increased activities of spermine oxidase (SMO) and acetyl polyamine oxidase (APAO) significantly, and reduced the levels of putrescine and spermidine. These data suggest a possible mechanism for the antiestrogenic effects of tamoxifen/endoxifen, involving the stimulation of polyamine oxidase enzymes. Therefore, SMO and APAO stimulation might be useful biomarkers for the efficacy of endoxifen treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)2293-2302
Number of pages10
JournalAmino Acids
Issue number10
StatePublished - Oct 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry


  • Acetyl polyamine oxidase
  • Endoxifen
  • MCF-7 breast cancer cells
  • Ornithine decarboxylase
  • Polyamines
  • S-adenosylmethionine decarboxylase
  • Spermine oxidase
  • Tamoxifen
  • Tff1


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