E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes
- Authors
- Lee, Shin-Hee; Hwang, Hye-Min; Pyo, Chul-Woong; Hahm, Dae Hyun; Choi, Sang-Yun
- Issue Date
- 6월-2010
- Publisher
- SPRINGER
- Keywords
- Lactoferrin; Iron; Apoptosis Jurkat; Bcl-2
- Citation
- BIOMETALS, v.23, no.3, pp.507 - 514
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMETALS
- Volume
- 23
- Number
- 3
- Start Page
- 507
- End Page
- 514
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/116275
- DOI
- 10.1007/s10534-010-9341-1
- ISSN
- 0966-0844
- 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.
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