title: Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer.
abstract: 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.
authors.affiliation: Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA. thomastj@rwjms.rutgers.edu.|Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA. thomastj@rwjms.rutgers.edu.
authors.forename: T J
authors.initials: TJ
authors.lastname: Thomas
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA.|Formerly Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.|, 40 Caldwell Drive, Princeton, NJ, 08540, USA.
authors.forename: Thresia
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA.
authors.forename: Shali
authors.initials: S
authors.lastname: John
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: PingAr
authors.initials: P
authors.lastname: Yang
authors.affiliation: School of Pharmacy, University of Eastern Finland, Biocenter Kuopio, P.O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Tuomo A
authors.initials: TA
authors.lastname: Keinänen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Biocenter Kuopio, P.O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Mervi T
authors.initials: MT
authors.lastname: Hyvönen
mesh_terms: D015317:Biogenic Polyamines / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015317:Biogenic Polyamines; D009363:Neoplasm Proteins; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D004958:Estradiol
keywords: Acetyl polyamine oxidase; Endoxifen; MCF-7 breast cancer cells; Ornithine decarboxylase; Polyamines; S-adenosylmethionine decarboxylase; Spermine oxidase; Tamoxifen; Tff1