PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo

Josef Michl, Bruce Scharf, Anna Schmidt, Chan Huynh, Raquibul Hannan, Hans Von Gizycki, Fred K. Friedman, Paul Brandt-Rauf, Robert L. Fine, Matthew R. Pincus

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1577-1585
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number7
DOIs
StatePublished - Oct 1 2006

Fingerprint

Pancreatic Neoplasms
Peptides
Growth
Neoplasms
PNC-28
Acinar Cells
Peritoneal Cavity
Tumor Cell Line
Nude Mice
Breast
Necrosis
Stem Cells
Epithelial Cells
Apoptosis

Keywords

  • Nude mice
  • p53
  • Pancreatic cancer
  • PNC-28 peptide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. / Michl, Josef; Scharf, Bruce; Schmidt, Anna; Huynh, Chan; Hannan, Raquibul; Von Gizycki, Hans; Friedman, Fred K.; Brandt-Rauf, Paul; Fine, Robert L.; Pincus, Matthew R.

In: International Journal of Cancer, Vol. 119, No. 7, 01.10.2006, p. 1577-1585.

Research output: Contribution to journalArticle

Michl, J, Scharf, B, Schmidt, A, Huynh, C, Hannan, R, Von Gizycki, H, Friedman, FK, Brandt-Rauf, P, Fine, RL & Pincus, MR 2006, 'PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo', International Journal of Cancer, vol. 119, no. 7, pp. 1577-1585. https://doi.org/10.1002/ijc.22029
Michl, Josef ; Scharf, Bruce ; Schmidt, Anna ; Huynh, Chan ; Hannan, Raquibul ; Von Gizycki, Hans ; Friedman, Fred K. ; Brandt-Rauf, Paul ; Fine, Robert L. ; Pincus, Matthew R. / PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. In: International Journal of Cancer. 2006 ; Vol. 119, No. 7. pp. 1577-1585.
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AU - Scharf, Bruce

AU - Schmidt, Anna

AU - Huynh, Chan

AU - Hannan, Raquibul

AU - Von Gizycki, Hans

AU - Friedman, Fred K.

AU - Brandt-Rauf, Paul

AU - Fine, Robert L.

AU - Pincus, Matthew R.

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N2 - 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.

AB - 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.

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