Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells.
The molecular mechanism of lactoferrin-induced cell growth inhibition is incompletely understood. Studying head and neck cancer cells treated with human lactoferrin, we observed growth arrest in three of four cell lines tested. This growth arrest was caused by cell cycle inhibition at the G0-G1 checkpoint. Lactoferrin-induced growth inhibition was associated with a large increase in p27 protein, accompanied by decreased phosphorylation of retinoblastoma protein, and suppression of cyclin E. Decreased levels of phosphorylated Akt were also observed in lactoferrin-sensitive cell lines after treatment. These findings suggest that in head and neck cancer cells the growth inhibitory effects of lactoferrin are mediated through a p27/cyclin E-dependent pathway that may be modulated in part by changes in Akt phosphorylation.
Xiao
Yan
Y
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Monitto
Constance L
CL
Minhas
Khalid M
KM
Sidransky
David
D
D018797:Cell Cycle Proteins / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D019927:Cyclin E; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D007781:Lactoferrin