PNC-27 (5mg)

Description

PNC-27 Peptide: Targeted Anti-Cancer Therapy

What is PNC-27 Peptide?

PNC-27 is a 27-amino acid peptide that may help reduce cancer cell activity and proliferation. It originates from the third helix of the α-helical segment of p53 (ASPP2), a tumor-suppressing protein. Research shows that PNC-27 may trigger necrosis, rather than apoptosis, in pancreatic cancer, ovarian cancer, leukemia, and other cancer cell lines.

PNC-27 seems to selectively target cancer cells, leaving healthy cells unaffected. First synthesized in 2000 during HIV research, it can bind the HDM-2 protein, often overexpressed in cancer cell membranes. This binding can form pores that disrupt the cell membrane, causing ion influx, cellular content leakage, and ultimately, cancer cell death.

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Chemical Makeup

• Molecular Formula: C188H293N53O44S

• Molecular Weight: 4031.7 g/mol

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Research and Clinical Studies

PNC-27 and Selective Cancer Cell Death

A 2009 study tested whether it interacts with non-cancerous cells. Researchers found that PNC-27 binds HDM-2 only in cancer cells. By forming a 1:1 complex with HDM-2, the peptide may initiate pore formation in the membrane. Electron microscopy revealed ring-shaped structures at the cancer cell surface, supporting selective toxicity. Normal cells did not show these structures unless HDM-2 was artificially introduced.

PNC-27 and Cancer Cell Membrane Lysis

A 2010 study examined how intact it induces membranolysis. Researchers tagged the peptide with fluorescent markers to track its structure. Bright yellow fluorescence appeared only in cancer cell membranes, indicating intact PNC-27 caused pore formation and released lactate dehydrogenase (LDH), a cell lysis marker. Healthy cells remained unaffected. The intact peptide is crucial for cytotoxic activity.

PNC-27 and Non-Solid Tumor Cells

In 2014, researchers studied it against non-solid tumor cells. Murine leukocyte controls confirmed the peptide targets HDM-2-expressing cancer cells, forming transmembrane pores and inducing necrosis. These effects occur even in leukemia cells lacking p53, suggesting a p53-independent pathway.

PNC-27 and Cancer Cell Growth

PNC-28, a peptide similar to PNC-27, has shown tumor suppression in ovarian cancer and mouse xenograft models, reducing tumor size. In 2020, PNC-27 demonstrated activity against acute leukemia cell lines (U937, OCI-AML3, HL60), targeting cells with high HDM-2 expression and promoting selective cancer cell death.

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Conclusion

PNC-27 is a promising peptide that selectively disrupts cancer cell membranes via HDM-2 binding, inducing necrosis without harming healthy cells. Its mechanism offers potential for targeted cancer therapies, including solid and non-solid tumors.

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References

1. 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/
2. 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