We report that amino acids 50 to 77 of azurin (p28) preferentially enter the human breast cancer cell lines MCF-7, ZR-75-1, and T47D through a caveolin-mediated pathway. Alth ough p28 enters p53 wild-type MCF-7 and the isogenic p53 dominant-negative MDD2 breast cancer cell lines, p28 only induces a G2-M-phase cell cycle arrest and apoptosis in MCF-7 cells.p2 8 exerts its antiproliferative activity by reducing proteasomal degradation of p53 through formation of a p28:p53 complex within a hydrophobic DNA-binding domain (amino acids 80-276), increasing p53 levels and DNA-binding activity.Subsequent elevation of the cyclin-dependent kinase inhibitors p21 and p27 reduces cyclin-dependent kinase 2 and cyclin A levels in a time-dependent manner in MCF-7 cells but not in MDD2 cells.T hese results suggest that p28 and similar peptides that significantly reduce proteasomal degradation of p53 by a MDM2-independent pathway(s) may provide a unique series of cytostatic and cytotoxic (apoptotic) chemotherapeutic agents. Copyright © 2009 American Association for Cancer Research.
CITATION STYLE
Yamada, T., Mehta, R. R., Lekmine, F., Christov, K., King, M. L., Majumdar, D., … Das Gupta, T. K. (2009). A peptide fragment of azurin induces a p53-mediated cell cycle arrest in human breast cancer cells. Molecular Cancer Therapeutics, 8(10), 2947–2958. https://doi.org/10.1158/1535-7163.MCT-09-0444
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