Bromodeoxyuridine Inhibits Cancer Cell Proliferation In Vitro and In Vivo

Levkoff, Lindsay H., Marshall II, Gregory P., Ross, Heather H., Caldeira, Maria, Reynolds, Brent A., Caldeira, Meryenm, Mariani, Christopher L., Streit, Wolfgang J. and Laywell, Eric D. (2008) Bromodeoxyuridine Inhibits Cancer Cell Proliferation In Vitro and In Vivo. Neoplasia, 10 8: 804-816. doi:10.1593/neo.08382

Author Levkoff, Lindsay H.
Marshall II, Gregory P.
Ross, Heather H.
Caldeira, Maria
Reynolds, Brent A.
Caldeira, Meryenm
Mariani, Christopher L.
Streit, Wolfgang J.
Laywell, Eric D.
Title Bromodeoxyuridine Inhibits Cancer Cell Proliferation In Vitro and In Vivo
Formatted title
Bromodeoxyuridine Inhibits Cancer Cell Proliferation In Vitro and In Vivo
Journal name Neoplasia   Check publisher's open access policy
ISSN 1522-8002
Publication date 2008-08
Year available 2008
Sub-type Article (original research)
DOI 10.1593/neo.08382
Open Access Status DOI
Volume 10
Issue 8
Start page 804
End page 816
Total pages 13
Editor Alnawaz Rehemtulla
Place of publication United States
Publisher Neoplasia Press
Collection year 2009
Language eng
Subject C1
920111 Nervous System and Disorders
1109 Neurosciences
Abstract The thymidine analog bromodeoxyuridine (BrdU) is incorporated into newly synthesized DNA and has been shown to increase the susceptibility of incorporating cells to ionizing radiation. However, in the absence of secondary stressors, BrdU is thought to substitute relatively benignly for thymidine and is commonly used to “birth-date” proliferative cells. We report a novel antiproliferative effect of BrdU on cancer cells, which is independent of its role in radiosensitization. A single, brief in vitro exposure to BrdU induces a profound and sustained reduction in the proliferation rate of all cancer cells examined. Cells do not die but variably up-regulate some senescence-associated proteins as they accumulate in the G1 phase of the cell cycle. Bromodeoxyuridine also impairs the proliferative capacity of primary tumor-initiating human glioma cells and may therefore represent a means of targeting cancer stem cells. Finally, conservative in vivo BrdU regimens—in the absence of any other treatment—significantly suppress the progression of gliomas in the highly aggressive, syngeneic RG2 model. These results suggest that BrdU may have an important role as an adjunctive therapeutic for a wide variety of cancers based on new insights into its effect as a negative regulator of cell cycle progression.
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Mon, 09 Mar 2009, 13:05:44 EST by Debra McMurtrie on behalf of Queensland Brain Institute