E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes.
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.
Lee
Shin-Hee
SH
School of Life Sciences and Biotechnology, Korea University, 5 Anam-dong, Sungbuk-gu, Seoul 136-701, Korea.
Hwang
Hye-Min
HM
Pyo
Chul-Woong
CW
Hahm
Dae Hyun
DH
Choi
Sang-Yun
SY
D017209:Apoptosis; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007781:Lactoferrin / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000473:pathology*; D014407:Tumor Cells, Cultured
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D007781:Lactoferrin