Preferential Induction of Necrosis in Human Breast Cancer Cells by a p53 Peptide Derived from the MDM2 Binding Site

Details

• Personal Author:
  Brandt-Rauf PW ; Cassai N ; Do TN ; Drew L ; Fine RL ; Friedman FK ; Michl J ; Petrylak DP ; Pincus MR ; Raffo AJ ; Rosal RV ; Sidhu G ; Szmulewicz J
• Description:
  p53 is the most frequently altered gene in human cancer and therefore represents an ideal target for cancer therapy. Several amino terminal p53-derived synthetic peptides were tested for their antiproliferative effects on breast cancer cell lines MDA-MB-468 (mutant p53), MCF-7 (overexpressed wild-type p53), and MDA-MB-157 (null p53). p53(15)Ant peptide representing the majority of the mouse double minute clone 2 binding site on p53 (amino acids 12-26) fused to the Drosophila carrier protein Antennapedia was the most effective. p53(15)Ant peptide induced rapid, nonapoptotic cell death resembling necrosis in all breast cancer cells; however, minimal cytotoxicity was observed in the nonmalignant breast epithelial cells MCF-10-2A and MCF-10F. Bioinformatic/biophysical analysis utilizing hydrophobic moment and secondary structure predictions as well as circular dichroism spectroscopy revealed an alpha-helical hydrophobic peptide structure with membrane disruptive potential. Based on these findings, p53(15)Ant peptide may be a novel peptide cancer therapeutic because it induces necrotic cell death and not apoptosis, which is uncommon in traditional cancer therapy. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Cytotoxins Genetics Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Breast Cancer Breast-cancer Cancer Cell-cultures Cytotoxicity Genes MDM2 Necrosis P53 Peptides
• ISSN:
  0950-9232
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  22
• Issue:
  10
• NIOSHTIC Number:
  nn:20029161
• Citation:
  Oncogene 2003 Mar; 22(10):1431-1444
• Email:
  pwb1@columbia.edu
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Work Environment and Workforce: Special Populations
• Performing Organization:
  Department of Environmental Health Sciences, The Mailman School of Public Health, Columbia University, New York, New York
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Oncogene
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:54b4ac09fcc97c56403385083ec68ba4c4aaf4d26665d8d295931378450ccbc3585c5eda784adf5f90a04a6fe0ac2bead07d2967ab7b35010f3845e49be33082
• Download URL:
  https://stacks.cdc.gov/view/cdc/190213/cdc_190213_DS1.pdf
• File Type:
  [PDF - 458.11 KB ]