Document Detail

Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand.
MedLine Citation:
PMID:  12721755     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Tamoxifen (TAM), a nonsteroidal anticancer agent, is used in the treatment of breast cancer. In the current study, we investigated whether TAM induces apoptosis in tumor cells by altering the expression of Fas and Fas ligand (FasL).
METHODS: Several tumor cell lines were used to test the ability of TAM to induce apoptosis, which was studied using the TUNEL assay. The effect of TAM on the expression of Fas and FasL was analyzed using a flow cytometer.
RESULTS: TAM was found to suppress the growth of an estrogen receptor-positive human mammary tumor cell line (T-47D) by inducing apoptosis. Interestingly, TAM also induced apoptosis in an estrogen receptor-negative murine T cell lymphoma cell line, EL-4. The ability of TAM to induce apoptosis in T-47D and EL-4 tumor cells correlated with the increased expression of FasL but not Fas on the tumor cells. Similar to TAM, a metalloproteinase (MP) inhibitor, which is known to increase the expression of membrane-bound FasL, was found to induce apoptosis in both T-47D and EL-4 tumor cells by increasing the expression of FasL but not Fas. Furthermore, both TAM and the MP inhibitor failed to induce apoptosis in L1210 tumor cell lines that failed to express FasL.
CONCLUSIONS: The current study demonstrates that TAM can induce apoptosis in Fas(+) tumor cells by upregulating FasL.
Nisha Nagarkatti; Barbara A Davis
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Publication Detail:
Type:  Journal Article     Date:  2003-03-27
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  51     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-30     Completed Date:  2003-06-27     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  284-90     Citation Subset:  IM    
Molecular Nutrition Laboratory, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
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MeSH Terms
Anticarcinogenic Agents / pharmacology*
Antigens, CD95 / biosynthesis*
Apoptosis / drug effects*
Breast Neoplasms / enzymology,  metabolism,  pathology
Dipeptides / pharmacology
Fas Ligand Protein
Leukemia L1210 / enzymology,  metabolism,  pathology
Lymphoma / enzymology,  metabolism,  pathology
Membrane Glycoproteins / biosynthesis*
Metalloendopeptidases / antagonists & inhibitors
Neoplasms / enzymology,  metabolism*,  pathology
Tamoxifen / pharmacology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Antigens, CD95; 0/Dipeptides; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; 0/Tnfsf6 protein, rat; 10540-29-1/Tamoxifen; EC 3.4.24.-/Metalloendopeptidases

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