The Potential Impact of PNC-27 on Malignant Cell Lysis

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PNC-27 peptide

Potential Impact of PNC-27 on Malignant Cell Lysis

This article will focus on PNC-27 and its involvement in extensive research on malignant cell lysis. Studies suggest PNC-27 is a peptide consisting of 27 amino acids that have been investigated for its possible role in reducing cancer cell activity. P53 (ASPP2) is derived from its third helical segment as a protein implicated in tumor suppression. It has been hypothesized that PNC-27 may cause programmed cell death (apoptosis and necrosis) in various cancer cell lines.


Animal models have suggested the peptide's promise, and studies have speculated that it may destroy cancer cells in low quantities. It has been suggested by researchers that PNC-27 may selectively kill cancer cells while not affecting healthy cells. The double minute (HDM2) protein, which is overexpressed on the membranes of the cancerogenic cells, has been speculated to demonstrate an excellent capacity to bond with this peptide, which was first created in 2000 to mitigate potential symptoms of HIV. Findings suggest this protein's binding may cause membrane lysis and pore formation in the cell membrane of cancer cells. This promotes apoptosis, often known as cell death, by allowing ions to enter and contents to leave the cell. [i]


PNC-27 Peptide Research and Clinical Investigations


PNC-27 Peptide and Selective Cell Death 

In 2009, researchers looked at whether or not presenting PNC-27 peptide to the body has any effects on cells that aren't malignant. Based on its structure, researchers reasoned that binding with the HDM-2 protein alone might kill cancer cells. Supposedly, HDM-2 protein is only found in malignant cells. In this experiment, the HDM-2 protein was introduced into normal cells taken from the organism. PNC-27 peptide, which normally might not affect the cells, was suggested to be toxic to the implanted cells. [ii]


PNC-27 Peptide and Malignant Cell Lysis

The creation of membrane holes was the focus of another study [iv] done in 2010, which sought to determine whether just certain segments of the peptide were responsible for this action. The peptide was induced for this investigation using a fluorescent reagent (green fluorescence at the amino group terminus and red fluorescence at the carboxyl group terminal). In order to determine the membrane coloration associated with membranolysis, this peptide was delivered to both breast tumors and normal cells. Bright yellow fluorescence was recorded following membrane lysis half an hour after adding the peptide, suggesting that the peptide was whole throughout the cellular membrane-killing process. This was seen only in cancer cells, whereas normal cells continued to thrive.


"PNC-27 may induce cancer cell membrane lysis by acting as the unmodified peptide, not fragments," wrote Kelley A. Sookraj et al. Research suggests PNC-27 may interact with the intramembrane aims of MCF-7 cells, which are not present in the membrane of the non-transformed cell line, causing the punctate yellow fluorescence. Because of this interaction, PNC-27 is thought to last longer. Since untransformed MCF-10-2A cells lack these targets in their membranes, the double-labeled peptide first fluoresces uniformly throughout their membranes before being destroyed. [iii]


PNC-27 Peptide and Cancer Cells

PNC-28, which is extremely similar to PNC-27 in structure and function, was the subject of a study [v]. Studies suggest the HDM-2 proteins in cancer cells seem to be the only targets of these p53-derived peptides. This work used ovarian cancer cells and a mouse xenograft model to test PNC-27's anti-tumor potential. Researchers hypothesized that PNC-27 may have decreased tumor size and slowed ovarian cancer progression in a mouse model.


Another research from 2020 aimed to test the potential of the PNC-27 peptide on leukemia cell lines that did not include stem cells [vi]. Scientists studied "acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia; and HL60, acute promyelocytic leukemia." The HDM-2 protein was suggested to be substantially expressed in all PNC-27 peptide-targeted leukemia cells after peptide presentation. [vi]


The purchase and use of the PNC-27 peptide is limited to researchers and laboratories. CorePeptides.com is a reputable platform for authorized researchers seeking to procure peptides for their studies.

The information presented in this article is intended solely for educational purposes.


References

[i] Davitt K, Babcock BD, Fenelus M, Poon CK, Sarkar A, Trivigno V, Zolkind PA, Matthew SM, Grin’kina N, Orynbayeva Z, Shaikh MF, Adler V, Michl J, Sarafraz-Yazdi E, Pincus MR, Bowne WB. The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. Ann Clin Lab Sci. 2014 Summer;44(3):241-8. PMID: 25117093. https://pubmed.ncbi.nlm.nih.gov/25117093/


[ii] Sarafraz-Yazdi E, Mumin S, Cheung D, Fridman D, Lin B, Wong L, Rosal R, Rudolph R, Frenkel M, Thadi A, Morano WF, Bowne WB, Pincus MR, Michl J. PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Biomedicines. 2022; 10(5):945. https://doi.org/10.3390/biomedicines10050945


[iii] Sookraj KA, Bowne WB, Adler V, Sarafraz-Yazdi E, Michl J, Pincus MR. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol. 2010 Jul;66(2):325-31. doi: 10.1007/s00280-009-1166-7. Epub 2010 Feb 25. PMID: 20182728. https://pubmed.ncbi.nlm.nih.gov/20182728/


[iv] Davitt K, Babcock BD, Fenelus M, Poon CK, Sarkar A, Trivigno V, Zolkind PA, Matthew SM, Grin’kina N, Orynbayeva Z, Shaikh MF, Adler V, Michl J, Sarafraz-Yazdi E, Pincus MR, Bowne WB. The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. Ann Clin Lab Sci. 2014 Summer;44(3):241-8. PMID: 25117093. https://pubmed.ncbi.nlm.nih.gov/25117093/


[v] Wilbur B. Bowne et al., The Penetratin Sequence in the Anti-cancer PNC-28 Peptide Causes Tumor Cell Necrosis Rather Than Apoptosis of Human Pancreatic Cancer Cells, Annals of Surgical Oncology 15(12):3588–3600 Published by Springer Science+Business Media, LLC  2008 The Society of Surgical Oncology, Inc. DOI: 10.1245/s10434-008-0147-0. https://webs.iiitd.edu.in/raghava/cancerppd/refpdf/18931881.pdf


[vi] Anusha Thadi et al, Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells, Anticancer Research 40 (9):4857-4867, September 2020

https://www.researchgate.net/publication/344117616_Targeting_Membrane_HDM-2_by_PNC-27_Induces_Necrosis_in_Leukemia_Cells_But_Not_in_Normal_Hematopoietic_Cells



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