A peroxisome proliferator-activated receptor-γ agonist and the p53 rescue drug CP-31398 inhibit the spontaneous immortalization of breast epithelial cells

Brittney-Shea Herbert, Virginia P. Pearce, Linda S. Hynan, Denise M. LaRue, Woodring E. Wright, Levy Kopelovich, Jerry W. Shay

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cell immortalization is a critical and rate-limiting step in cancer progression. Agents that inhibit cell immortalization may have utility for novel molecular chemopreventive strategies. Preimmortal breast epithelial cells derived from a patient with the Li-Fraumeni Syndrome (LFS) can spontaneously immortalize in vitro at a measurable and reproducible frequency. In the present study, these cells were treated in vitro with low (nM) concentrations of potential and otherwise clinically validated chemopreventive agents, including several nonsteroidal anti-inflammatory drugs, rosiglitazone maleate, and the p53 rescue drug CP-31398. Rosiglitazone maleate (P <0.05) and CP-31398 (P <0.05) significantly inhibited the frequency of spontaneous immortalization of LFS breast epithelial cells compared with untreated controls. Nonsteroidal anti-inflammatory drugs, including specific cyclooxengenase-2 inhibitors, only moderately inhibited the spontaneous immortalization of preimmortal LFS breast epithelial cells. The significant effects of the p53 rescue drug CP-31398 correlated with the increase in cellular death induced by telomere shortening-induced DNA damage signals, including increases in p53 and p21 protein levels. Because immortalization is one step in cancer progression, these studies show the potential usefulness of a cell-based model system to screen the effects of known and potentially novel chemopreventive agents, using cell immortalization as an end point.

Original languageEnglish (US)
Pages (from-to)1914-1919
Number of pages6
JournalCancer Research
Volume63
Issue number8
StatePublished - Apr 15 2003
Externally publishedYes

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Drug Repositioning
Peroxisome Proliferator-Activated Receptors
rosiglitazone
Li-Fraumeni Syndrome
Breast
Epithelial Cells
Anti-Inflammatory Agents
Telomere Shortening
Pharmaceutical Preparations
DNA Damage
Neoplasms
CP 31398
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A peroxisome proliferator-activated receptor-γ agonist and the p53 rescue drug CP-31398 inhibit the spontaneous immortalization of breast epithelial cells. / Herbert, Brittney-Shea; Pearce, Virginia P.; Hynan, Linda S.; LaRue, Denise M.; Wright, Woodring E.; Kopelovich, Levy; Shay, Jerry W.

In: Cancer Research, Vol. 63, No. 8, 15.04.2003, p. 1914-1919.

Research output: Contribution to journalArticle

Herbert, Brittney-Shea ; Pearce, Virginia P. ; Hynan, Linda S. ; LaRue, Denise M. ; Wright, Woodring E. ; Kopelovich, Levy ; Shay, Jerry W. / A peroxisome proliferator-activated receptor-γ agonist and the p53 rescue drug CP-31398 inhibit the spontaneous immortalization of breast epithelial cells. In: Cancer Research. 2003 ; Vol. 63, No. 8. pp. 1914-1919.
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