PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo.
Michl J; Scharf B; Schmidt A; Huynh C; Hannan R; von Gizycki H; Friedman FK; Brandt-Rauf P; Fine RL; Pincus MR
Int J Cancer 2006 Oct; 119(7):1577-1585
PNC-28 is a p53 peptide from its mdm-2-binding domain (residues 17-26), which contains the penetratin sequence enabling cell penetration on its carboxyl terminal end. We have found that this peptide induces necrosis, but not apoptosis, of a variety of human tumor cell lines, including several with homozygous deletion of p53, and a ras-transformed rat acinar pancreatic carcinoma cell line, BMRPA1. Tuc3. On the other hand, PNC-28 has no effect on untransformed cells, such as rat pancreatic acinar cells, BMRPA1, and human breast epithelial cells and no effect on the differentiation of human stem cells. In this study, we now test PNC-28 in vivo for its ability to block the growth of BMRPA1. Tuc3 cells. When administered over a 2-week period in the peritoneal cavities of nude mice containing simultaneously transplanted tumors, PNC-28 causes complete destruction of these tumors. When delivered concurrently with tumor explantation at a remote site, PNC-28 causes a complete blockade of any tumor growth during its 2-week period of administration and 2 weeks posttreatment, followed by weak tumor growth that plateaus at low tumor sizes compared with tumor growth in the presence of a control peptide. When administered after tumor growth has occurred at a site remote from the tumor, PNC-28 causes a decrease in tumor size followed by a slow increase in tumor growth that is significantly slower than growth in the presence of control peptide. These results suggest that PNC-28 may be effective in treating cancers especially if delivered directly to the tumor.
Cancer; Pancreatic-islets-neoplasms; Animal-studies; Animals; Laboratory-animals; Tumors; Peptides; Proteins; Dose-response; Neoplasms; Carboxylic-acids; Amino-acids; Cell-function; Cell-migration; Antitumor-agents; Bioassays; Carcinomas; In-vivo-study; Tumor-inhibition;
Author Keywords: PNC-28 peptide; p53; pancreatic cancer; nude mice
Josef Michl, Department of Pathology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
Research Tools and Approaches: Cancer Research Methods
International Journal of Cancer
Columbia University Health Sciences