PNC-27

Structure

PNC-27 contains a segment from human p53, residues 12–26, that is involved in the binding of p53 to HDM-2 connected to a membrane penetrating sequence called the membrane residency peptide (MRP). The sequence is H-Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu-Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly-OH[3].

Description

PNC-27 is an anti-cancer peptide that, in small in-vitro studies, has been shown to induce tumour cell necrosis. It is not currently approved for use in the United States (U.S.) and is currently being marketed online as a non-toxic potential cure for various cancers. Recently, the FDA issued warnings to the public regarding PNC-27 use, suggesting possible contamination and unknown side effects of the treatment. PNC-27 may be available in various dosage forms, such as a nebulized solution, intravenous solution, vaginal suppository, or rectal suppository. FDA has not evaluated or approved PNC-27 as safe and effective in treating any disease, including cancer[1].

Definition

PNC-27 is an anticancer peptide, containing an HDM-2-binding domain. PNC-27 shows anti-tumor activity and can be used in acute myeloid leukemia research.

in vitro

PNC-27 (50 μg/mL; 0-3 h) induces cancer cell death.
PNC-27 (50 μg/mL; 15 min) binds to cell membrane-bound HDM-2.

in vivo

PNC-27 (intraperitoneal injection; 40 mg/kg; once daily; 2-3 w) shows anti-leukemia activity in vivo.

Mode of action

PNC-27 and its shorter analogue peptide (PNC-28) are peptides that selectively lyse the membranes of cancer cells, resulting in the necrosis of a variety of cancer cell lines and primary human tumours, but not untransformed cells. It is a membrane-active peptide that binds to the HDM-2 protein expressed in the cancer cell membranes of solid tissue tumour cells and induces transmembrane pore formation in cancer, but not in normal cells, resulting in tumour cell necrosis that is independent of p53 activity in these cells. PNC-27 contains residues 12–26 of the HDM-2-binding domain of p53 attached to a leader sequence (termed the membrane residency peptide or MRP) that usually induces the transport of peptides attached to it across the cell and nuclear membranes. The research found that this peptide induced rapid necrosis of cancer cells rather than apoptosis. Induction of tumour cell necrosis was not induced by the isolated p53 12–26 peptide, by the leader sequence alone, or by both separate peptides together, suggesting that both domains must be covalently linked for tumour cell killing[2].

References

[1] Aguon, P. M. et al. “Experimental PNC-27 Therapy and Massive GI Hemorrhage: A Complication or Coincidence?: 1879.” The American Journal of Gastroenterology 7 1 (2017): 0.
[2] Katlin Davitt. “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.” Annals of clinical and laboratory science 44 3 (2014): 241–8.
[3] Ehsan Sarafraz‐Yazdi. “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).