While past efforts to restore tumor suppressor function in cancer cells have focused on gene therapy, Dowdy and colleagues introduced modified p53 peptides (parts of the protein) into cancer cells. p53 works as a "transcriptional" activator that binds to specific gene sequences and triggers apoptosis in response to DNA damage. One region of the p53 protein, the C-terminal domain, facilitates DNA binding. In cancer cells, synthesized peptides (called p53C) derived from this region can induce apoptosis by restoring function to p53 proteins with DNA-binding mutations.
To get p53C peptides into cancer cells, the scientists used a technique pioneered by Dowdy that delivers proteins into the cell interior. Since the cell membrane normally limits passage to only small molecules (larger molecules generally enter through surface receptors), this is no small feat. Testing the effectiveness of the peptide therapy on mouse strains that model human metastatic disease, the scientists found that mice treated with the p53C peptide showed a significant reduction in tumor mass and lived six times longer than mi
Contact: Barbara Cohen
Public Library of Science