BACKGROUND: Lactoferrin (Lf), an iron-binding protein present in mammalian secretions, plays important roles in cancer prevention by inducing apoptosis. MATERIALS AND METHODS: PC-14 lung adenocarcinoma cells were exposed to bovine Lf (bLf) protein and the expression of caspase-3 and apoptosis protease-activating factor-1 (APAF-1) was assessed. To investigate the molecular mechanism of apoptosis induced by bLf, a major Lf-binding protein was screened using a protein microarray with bLf protein as the probe. Protein interaction was demonstrated by co-immunoprecipitation, immunofluorescence and phosphatase activity assay. RESULTS: Lf directly suppressed the proliferation of the PC-14 cells by triggering their apoptosis. Lf was shown to bind specifically with a 36-kDa protein, immunoglobulin (CD79A)-binding protein 1 (IGBP1). The binding complex interacted with the catalytic subunit of protein phosphatase 2A (PP2A), thus reducing the phosphatase activity of PP2A and triggering apoptosis. CONCLUSION: Lf binds IGBP1 and promotes the acceleration of cellular apoptosis.
BACKGROUND: Lactoferrin (Lf), an iron-binding protein present in mammalian secretions, plays important roles in cancer prevention by inducing apoptosis. MATERIALS AND METHODS:PC-14 lung adenocarcinoma cells were exposed to bovine Lf (bLf) protein and the expression of caspase-3 and apoptosis protease-activating factor-1 (APAF-1) was assessed. To investigate the molecular mechanism of apoptosis induced by bLf, a major Lf-binding protein was screened using a protein microarray with bLf protein as the probe. Protein interaction was demonstrated by co-immunoprecipitation, immunofluorescence and phosphatase activity assay. RESULTS: Lf directly suppressed the proliferation of the PC-14 cells by triggering their apoptosis. Lf was shown to bind specifically with a 36-kDa protein, immunoglobulin (CD79A)-binding protein 1 (IGBP1). The binding complex interacted with the catalytic subunit of protein phosphatase 2A (PP2A), thus reducing the phosphatase activity of PP2A and triggering apoptosis. CONCLUSION: Lf binds IGBP1 and promotes the acceleration of cellular apoptosis.
Authors: Bi-Qing Li; Jin You; Lei Chen; Jian Zhang; Ning Zhang; Hai-Peng Li; Tao Huang; Xiang-Yin Kong; Yu-Dong Cai Journal: Biomed Res Int Date: 2013-05-22 Impact factor: 3.411