E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes

Shin Hee Lee, Hye Min Hwang, Chul Woong Pyo, Dae Hyun Hahm, Sang-Yun Choi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Lactoferrin (Lf) has been shown to control the proliferation of a variety of mammalian cells. Recently, we reported that human Lf induces apoptosis via a c-Jun N-terminal kinases (JNK)-associated Bcl-2 pathway that stimulates programmed cell death. In order to gain insight into the mechanism underlying Lf-triggered apoptotic features, we attempted to determine the mechanisms whereby the Lf-induced Bcl-2 family proteins exert their pro- or anti-apoptotic effects in Jurkat leukemia T lymphocytes. Treatment of the cells with high concentrations of Lf resulted in a significant reduction in in vitro growth and cell viability. As the levels of Lf increased, greater quantities of CDK6 and hyper-phosphorylated retinoblastoma protein were produced, resulting in the induction of E2F1-dependent apoptosis. Simultaneously, PARP and caspases were efficiently cleaved during Lf-induced apoptosis. The E2F1-induced apoptotic process occurred preferentially in p53-deficient Jurkat leukemia cells. Therefore, we attempted to determine whether E2F1-regulated Bcl-2 family proteins involved in the apoptotic process were relevant to Lf-induced apoptosis. We found that Lf increased the interaction of Bcl-2 with the pro-apoptotic protein Bad, whereas the total protein levels did not change significantly. Our results, collectively, suggest that Lf exploits the control mechanism of E2F1-regulated target genes or Bcl-2 family gene networks involved in the apoptotic process in Jurkat human leukemia T lymphocytes.

Original languageEnglish
Pages (from-to)507-514
Number of pages8
JournalBioMetals
Volume23
Issue number3
DOIs
Publication statusPublished - 2010 Jun 1

Keywords

  • Apoptosis
  • Bcl-2
  • Iron
  • Jurkat
  • Lactoferrin

ASJC Scopus subject areas

  • Biomaterials
  • Metals and Alloys
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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