Document Detail


Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake.
MedLine Citation:
PMID:  20383709     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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 [(3)H]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.
Authors:
Valentina K Todorova; Yihong Kaufmann; Shaoke Luo; V Suzanne Klimberg
Related Documents :
23152529 - Herpes simplex virus 2 (hsv-2) prevents dendritic cell maturation, induces apoptosis, a...
24454859 - Mir-24 regulates intrinsic apoptosis pathway in mouse cardiomyocytes.
9561849 - Oxygen radicals and signaling.
24367369 - Molecular mechanisms of differentiation of murine pro-inflammatory γδ t cell subsets.
23785289 - The xanthomonas campestris type iii effector xopj targets the host cell proteasome to s...
12607819 - 2,3,7,8-tetrachlorobenzo-p-dioxin inhibits proliferation of sk-n-sh human neuronal cell...
17352259 - Morin inhibits the growth of human leukemia hl-60 cells via cell cycle arrest and induc...
21991369 - Genetic ablation of cd68 results in mice with increased bone and dysfunctional osteocla...
23152529 - Herpes simplex virus 2 (hsv-2) prevents dendritic cell maturation, induces apoptosis, a...
Publication Detail:
Type:  Journal Article     Date:  2010-04-11
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  67     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  285-91     Citation Subset:  IM    
Affiliation:
Department of Surgery/Breast Surgical Oncology, University of Arkansas for Medical Sciences, 4301W. Markham St., Mail Slot 725, Little Rock, AR, 72205, USA, todorovavalentinak@uams.edu.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A novel bis-indole destabilizes microtubules and displays potent in vitro and in vivo antitumor acti...
Next Document:  The influence of space dimension on the large-time behavior in a reaction-diffusion system modeling ...