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Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):889-95. doi: 10.1016/j.ijrobp.2009.09.052.

Differential radiosensitizing effect of valproic acid in differentiation versus self-renewal promoting culture conditions.

Author information

  • 1Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

PURPOSE:

It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres.

METHODS AND MATERIALS:

We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cell transcription factors.

RESULTS:

3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA radiosensitized adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres.

CONCLUSION:

We have concluded that VA might preferentially radiosensitize differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and radiosensitizers.

Copyright (c) 2010 Elsevier Inc. All rights reserved.

PMID:
20159363
[PubMed - indexed for MEDLINE]
PMCID:
PMC2892870
Free PMC Article

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