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Cancer Chemotherapy and Pharmacology

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01.02.2011 | Original Article

Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake

verfasst von: Valentina K. Todorova, Yihong Kaufmann, Shaoke Luo, V. Suzanne Klimberg

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2011

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Abstract

Purpose

Modulation of estrogen receptor (ER) plays a central role in selective estrogen receptor modulators (SERMs) molecular mechanism of action, although studies have indicated that additional, non-ER-mediated mechanisms exist. It has been suggested that the induction of oxidative stress by SERM could be one of the non-ER-mediated mechanisms held responsible for their pro-apoptotic role in ER-negative cells. Tumor cells are known for their high requirement of glutamine (Gln) that serves multiple functions within the cells, including nutritional and energy source, as well as one of the precursors for the synthesis of natural antioxidant glutathione (GSH). We hypothesized that one of the mechanisms responsible for ER-independent anti-neoplastic properties of SERMs and also for their adverse side effects could be dependent on the inhibition of Gln uptake.

Methods

Human ER-negative MDA-MB231 breast cancer cells were treated with different doses of Tam and Ral. Gln uptake was monitored by using [³H]Gln assay. The effect of Tam and Ral on Gln transporter ASCT2 expression, glutathione (GSH) levels and cellular proliferation was determined.

Results

Tam and Ral inhibited Gln uptake in a dose-dependent manner through inhibition of ASCT2 Gln transporter. This effect of the anti-estrogens was associated with inhibition of GSH production and apoptosis. Treatment of cells with N-acetyl L-cysteine and 17 beta-estradiol 2 reversed the effects of Ral and Tam.

Conclusions

Our results indicate that one of the mechanisms of action (and possibly some of the side effects) of TAM and RAL is associated with inhibition of cellular Gln uptake, oxidative stress and induction of apoptosis.

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Titel: Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake
verfasst von: Valentina K. Todorova
Yihong Kaufmann
Shaoke Luo
V. Suzanne Klimberg
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2011
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1316-y

Neu im Fachgebiet Onkologie

18.04.2024 | Wirbelsäulenmetastase | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

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Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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