Journal article
HDM-2-Targeting Peptide PNC-27 Kills Cervical Cancer Cells but not Normal Cervical Cells
Annals of clinical and laboratory science, v 55(3), p347
May 2025
PMID: 40750238
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The peptide PNC-27 has been found to kill many different endodermal solid tissue and hematopoietic cancer cells but has no effect on normal cells. The mechanism involves binding to the HDM-2 protein, which is expressed in the membranes of cancer cells but not in normal (untransformed) cells. Our objectives in the current study are to determine 1) if PNC-27 is lethal to squamous cervical epithelial cancer cells but not to untransformed squamous cervical cells; 2) if membrane-bound HDM-2 is expressed uniquely in cervical cancer cells; and 3) whether HDM-2 is stable for detection in different types of preservative solutions.
We determined dose response curves for incubation of PNC-27 with the human squamous cervical cancer cell line HTB-35 (also called SiHa cells) and with the untransformed human squamous cervical cell line, PCS-480. Cell viability was determined using the MTT and LDH release assays. Finally, slot blots and flow cytometry were used to determine membrane expression of HDM-2 using a polyclonal anti-HDM-2 antibody.
We found that PNC-27 is cytotoxic even at low doses (IC
=12.4 μM) to the human HTB-35 cervical cancer squamous epithelial cell line but not to a counterpart normal human PCS-480 cell line. We found that HTB-35 cells express high levels of HDM-2 proteins in their membranes both in cell culture and in alcoholic preservative solutions but that the normal PCS-480 cells do not. Consistent with previous results, the data suggest that cervical cancer cells express HDM-2 in their membranes and that this is the target for PNC-27.
PNC-27 kills cervical squamous cancer but not normal cervical cells due to the unique expression of HDM-2 in the cervical squamous cell membranes. Thus, PNC-27 may be an effective drug against this cancer. Our results further suggest that the expression of membrane-bound HDM-2 on cervical cancer cells is stable both in cell culture media and in alcoholic preservative fluid.
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Details
- Title
- HDM-2-Targeting Peptide PNC-27 Kills Cervical Cancer Cells but not Normal Cervical Cells
- Creators
- Patryck K Krzesaj - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USAShabnam Seydafkan - Department of Pathology, Langone New York University Medical Center, New York, NY, USAAnna I Miller - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USAHui Ting Chen - Mirimus Laboratories, Brooklyn, NY, USAPrem Premsrirut - Mirimus Laboratories, Brooklyn, NY, USAAlfred Shim - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USASteven Mcglinchey - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USAEhsan Yazdi - Nomocan Pharmaceuticals, New York, NY, USA ehsan.yazdi@nomocanPaul Brandt-Rauf - School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USAMiriam Silberstein - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USAGholamali Jahari - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USARichard D Feinman - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USA richard.feinman@downstate.eduMatthew R Pincus - Departments of Pathology and Cell Biology, SUNY Health Sciences University, Brooklyn, NY, USA mrpincus2010@gmail.com
- Publication Details
- Annals of clinical and laboratory science, v 55(3), p347
- Publisher
- ASSOC CLINICAL SCIENTISTS
- Number of pages
- 7
- Grant note
- Nutrition and Metabolism Society, Inc.Research Foundation of the State University of New York
We are grateful to the Nutrition and Metabolism Society, Inc. and the Research Foundation of the State University of New York for financial support.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001551682400005
- Scopus ID
- 2-s2.0-105012910389
- Other Identifier
- 991022073152704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medical Laboratory Technology