Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer
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- 作者：T. J. Thomas ; Thresia Thomas ; Shali John ; Hui-Chen Hsu ; PingAr Yang…
- 关键词：Acetyl polyamine oxidase ; Endoxifen ; MCF ; 7 breast cancer cells ; Ornithine decarboxylase ; Polyamines ; S ; adenosylmethionine decarboxylase ; Spermine oxidase ; Tamoxifen ; Tff1
- 刊名：Amino Acids
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：48
- 期：10
- 页码：2293-2302
- 全文大小：771 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Biochemistry
Analytical Chemistry
Biochemical Engineering
Life Sciences
Proteomics
Neurobiology - 出版者：Springer Wien
- ISSN：1438-2199
- 卷排序：48
文摘
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.