The PNC-27 peptide is a scientifically developed compound hypothesized to target and eliminate cancer cells. This peptide belongs to the PNC family of investigational proteins. Its purpose is believed to specifically target cancerous cells, causing them to undergo cell necrosis while leaving normal cells unaffected.
PNC-27 comprises a binding domain that shares similarities with P53 residues 12-26 and a portion that may penetrate through cell membranes. Research has suggested that the PNC-27 peptide may bind to cancerous cells and cause their demise by breaking the cell membrane through membrane lysis.
PNC-27 Peptide: Mechanism of Action
Research suggests that PNC-27 was created to be employed in studies related to HIV. Still, its remarkable potential observed in these studied to selectively eliminate cancer cells while sparing normal cells has led to a shift in its intended research avenues.
Investigations purport that the PNC-27 peptide may exhibit non-toxic properties and selectively target cancer cells. PNC-27 is proposed to interact with the membranes of cancer cells, resulting in the appearance of openings. As a result of the variation in osmotic pressure, the holes lead to a swift implosion, causing the cells to perish instantly.
HDM-2 is present in the cell membranes of cancer cells. Upon presentation of PNC-27, the peptide seems to swiftly attach itself to the HDM-2 peptide located in the plasma membrane of cancerous cells. PNC-27 is purported to be responsible for causing damage by triggering membrane lysis, resulting in the demise of cancer cells through its interaction with HDM-2 peptides.
PNC-27 Peptide Studies
In a 2010 research paper issued by the American Association for Cancer, Dr. Ehsan Sarafraz-Yazdi and several other researchers discussed the impact and potential of PNC-27 within cancer research.
The study’s authors speculate that PNC-27 may work by creating oligomeric pores in the plasma membrane of tumor cells. Cells that have not undergone any changes or are not cancerous do not create oligomeric pores. They hypothesized that the selectivity of PNC-27 on cancer cells may be due to the mis-localization of MDM2 to the plasma membranes of cancerous cells.
Scientists believe these hypotheses describe the specific localization of MDM2 variants in cancer cell plasma membranes. Based on this understanding, it is widely believed that the PNC-27 peptide may have potential as a future anti-cancer compound that may at some point undergo clinical review, though none has been completed yet.
PNC-27 Peptide and Pain
As suggested by scientific research conducted on animal samples, it has been speculated that the peptide may potentially alleviate pain levels for up to one week following presentation. The animal samples appeared to exhibit flu-like symptoms during the third week of exposure, suggesting that the animal’s immune system responds to the demise of cancerous cells.
Findings implied that during the sixth week of the PNC-27 presentation, there appeared to be an increase in bilirubin and lactate dehydrogenase levels. During the tenth week, the tumors have been hypothesized to undergo a softening process and become more flexible, leading to a notable tumor breakdown.
The size of the tumor may increase significantly by the tenth week. Though this may be a result of inflammation caused by the immune system’s reaction. In the third month, investigations purported that animals seemed to experience a boost in their energy levels, while symptoms related to cancer indicated a noticeable decrease.
The findings from the PNC-27 experimental trials suggest the potential impact of the peptide on the cell membranes of cancerous cells. In addition, the cells surrounding the cancerous cells appeared to remain unaffected and maintained their functionality. In addition, studies have purported that PNC-27 may impact certain indicators found in the membranes of cancer cells. Furthermore, it has been hypothesized that PNC-27 may exhibit a prolonged half-life through this particular mode of action.
PNC-27 Peptide and Cancer Cells
As scientific research suggests, PNC-27 has been speculated to impede the growth of pancreatic cancer cells in vitro. Research suggests that PNC-27 may induce necrosis rather than apoptosis in various tumor cell lines, such as the BMRPA—ras transformed rat acinar pancreatic carcinoma cell line. It is worth mentioning that PNC-27 may have no impact on noncancerous cells. Based on scientific research, it was purported that the peptide may have effectively halted the growth of tumors during the second week of presentation and the following week. As a result, the tumor cells exhibited minimal growth and reached a small size, in contrast to the significant growth speculated when the peptide was absent.
Presentation of PNC-27 after the emergence of tumor growth at a distant location appeared to lead to a reduction in tumor size, followed by a gradual increase in tumor growth.
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References
[i] Sarafraz-Yazdi E, Bowne WB, Adler V, Sookraj KA, Wu V, Shteyler V, Patel H, Oxbury W, Brandt-Rauf P, Zenilman ME, Michl J, Pincus MR. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1918-23. doi: 10.1073/pnas.0909364107. Epub 2010 Jan 11. PMID: 20080680; PMCID: PMC2836618.
[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 Apr 20;10(5):945. doi: 10.3390/biomedicines10050945. PMID: 35625682; PMCID: PMC9138867.
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[v] Thadi A, Lewis L, Goldstein E, Aggarwal A, Khalili M, Steele L, Polyak B, Seydafkan S, Bluth MH, Ward KA, Styler M, Campbell PM, Pincus MR, Bowne WB. Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells. Anticancer Res. 2020 Sep;40(9):4857-4867. doi: 10.21873/anticanres.14488. PMID: 32878773.
