PNC-27 30mg

▎PNC 27 Structure

▎PNC 27 Research

What are the applications of PNC-27?

1, Treatment of leukemia: 

PNC-27 is able to bind HDM-2 protein on the membrane of cancer cells and induce the formation of cytotoxic transmembrane pores. In a study of human non-stem cell acute myeloid leukemia cell lines, HDM-2 was found to be highly expressed in the membranes of U937 (acute monocytic leukemia), OCI-AML3 (acute granulomonocytic leukemia), and HL60 (acute promyelocytic leukemia) cells.PNC-27 binds to HDM-2 on membranes, and induces necroptosis and LDH (lactate dehydrogenase) release within 4 hours. (LDH) release within 4 hours. Targeting HDM-2 on the cell membrane may be a potential strategy for the treatment of leukemia.PNC-27 exhibited significant anti-leukemic activity in several leukemia cell lines by targeting Membrane HDM-2 ^[1].

2. Induces tumor cell lysis

Acts as an intact peptide: 

Several studies have shown that PNC-27 induces tumor cell lysis as an intact peptide rather than as a fragment. For example, in a study of MCF-7 breast cancer cells and untransformed MCF-10-2A mammary epithelial cells, cells were treated with PNC-27 with green fluorescently labeled amino terminus and red fluorescently labeled carboxy terminus. The results showed a distinct punctate yellow fluorescence on the cancer cell membrane at 30 min, indicating that the intact peptide was present on the cancer cell membrane and increased with cancer cell lysis. In contrast, untransformed MCF-10-2A cells initially showed uniform yellow membrane fluorescence, but then disappeared. Unlike cancer cells, these untransformed cells remained viable. This suggests that PNC-27 induces membrane cleavage in cancer cells by acting as an entire peptide, rather than a fragment^[2].

Binding to HDM-2 to form pore structures: 

PNC-27 contains an HDM-2-binding structural domain and a cell-penetrating peptide (CPP) presequence, which induces the formation of pore structures by binding to HDM-2 on the cell membrane, leading to tumor cell lysis and necrosis. Conformational energy calculations showed that PNC-27 forms a complex with HDM-2 in a 1:1 ratio, with the leading sequence pointing away from the complex. Immunoscanning electron microscopy studies revealed the presence of multiple 6 nm and 15 nm labeled gold particles at a ratio of approximately 1:1 in the pores on the surface of cancer cells treated with PNC-27, suggesting that these complexes are important for pore structure. In contrast, no pores were formed in control, untransformed fibroblasts treated with PNC-27^[3].

Pancreatic Cancer: 

The novel anticancer PNC-27 peptide induces necrosis of human pancreatic MiaPaCa-2 cancer cells in a dose-dependent manner, but is non-toxic to normal cells. Studies have shown that PNC-27, when combined with Gemzar, a chemotherapeutic agent used to treat pancreatic cancer, has a greater cytotoxic effect on MiaPaCa-2 cells than Gemzar or PNC-27 alone. This may be because the PNC-27-induced pores increase the permeability of cancer cells to Gemzar, allowing more Gemzar to target cancer cells ^[1].

Ovarian Cancer: 

In ovarian cancer cell lines SKOV-3 and OVCAR-3, HDM-2 protein is highly expressed at the cell membrane.PNC-27 co-localizes with HDM-2 at the cell membrane, leading to rapid cell necrosis. In contrast, in the non-transformed control cell line HUVEC, co-localization and cytotoxicity of PNC-27 was not observed due to minimal membrane HDM-2 expression^[1].

Colon Cancer: 

PNC-27 selectively kills colon cancer stem cells. In six colon cancer cell lines, PNC-27 co-localized with membrane HDM-2 and caused cell death (tumor cell necrosis, high LDH release, membrane associated protein V and cysteine 3 negativity) only in cancer cells. In vivo, PNC-27 causes necrosis of tumor nodules but does not affect normal tissue ^[1].

3. Improved anti-tumor efficacy

Binding to Doxil: 

It has been found that PNC27 peptide, as a targeting ligand, can significantly enhance the anti-tumor efficacy of Doxil in HDM2-positive cancer cells. Different amounts of PNC27 peptide were inserted into Doxil, and flow cytometry and confocal analysis were performed on C26 colon cancer (HDM2-positive) and B16F0 melanoma (HDM2-negative) cells. The results showed that PNC27-Doxil exhibited significant cellular uptake and cytotoxicity in C26 cells, whereas these results were not observed in B16F0 cells. For example, PNC27-Doxil (100 PNC27 peptide) significantly increased the therapeutic efficacy of Doxil without affecting its biodistribution in C26 tumors ^[4].

4. Synergistic treatment of ovarian cancer with paclitaxel

Paclitaxel is widely used in the treatment of gynecological malignancies, but it targets tumor cells in the M phase of the cell cycle, with cells in other phases surviving and potentially leading to tumor recurrence.PNC-27 is a peptide synthesized from amino acids in the P53-MDM-2 binding domain that kills various cancer cell lines in a dose-dependent manner. Ovarian cancer ID8 cells exposed to paclitaxel were found to show increased expression of MDM-2 and increased sensitivity to PNC-27.The cytotoxic effect of PNC-27 is dependent on its binding to MDM-2, and blocking MDM-2 inhibits the killing effect of PNC-27. The heterodrug images of the dose combinations were synergistic, suggesting a synergistic effect between PNC-27 and paclitaxel ^[5]. In an intraperitoneal model of ovarian cancer (ID8), the addition of PNC-27 to weekly paclitaxel administration significantly reduced tumor growth. These data demonstrate a synergistic effect between PNC-27 and paclitaxel, with PNC-27 targeting cell-surviving paclitaxel and improving its antitumor effects.

5. Treatment of primary epithelial ovarian cancer

A study has established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinoma. One of them was from mucinous cystadenocarcinoma and the other was from high-grade papillary plasmacytoid carcinoma. The therapeutic efficacy of PNC-27 was quantitatively assessed by qualitative light microscopic observation and MTT cell proliferation assay as well as measurement of lactate dehydrogenase (LDH). The results showed that PNC-27 inhibited the growth of human primary cancer cells freshly isolated from two ovarian epithelial carcinomas in a dose-dependent manner and was cytotoxic to them. The control peptide PNC-29 had no effect on primary cancer cells. In addition, PNC-27 is also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines^[6].

In summary, PNC-27, as a novel anticancer peptide, shows significant potential for application in a variety of cancer therapies. In the field of leukemia, PNC-27 exhibited selective killing effects on acute myeloid leukemia (e.g., U937, OCI-AML3, and HL60 cell lines) and p53-deficient K562 cells, and achieved highly efficient antitumor effects by inducing cell necrosis and lactate dehydrogenase release. In the treatment of ovarian cancer, the combination of PNC-27 and paclitaxel showed a synergistic effect, which could significantly inhibit tumor growth and still have killing activity against chemotherapy-resistant cells. In addition, the combination of PNC-27 with liposomal drugs (e.g. Doxil) as a targeting ligand can enhance the specific delivery and anti-tumor efficacy of the drug to HDM2-positive tumor cells. Its inhibitory effect on primary epithelial ovarian cancer progenitor cells further validates the clinical translational value. Currently, PNC-27 has entered phase I clinical trials, and more clinical studies are needed to validate its safety and long-term efficacy, so as to promote it as an innovative solution for cancer treatment.

About The Author

The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.

Scientific Journal Author

Sarafraz-Yazdi E is a researcher associated with several organizations, including NomoCan, New York Blood Center, SUNY Downstate Health Sciences University, and New York Harbor VA Med Ctr. These affiliations highlight his involvement in diverse research and medical environments.

His research interests span across various subject categories such as Oncology, Medical Laboratory Technology, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, and Research & Experimental Medicine. His work in these fields reflects his broad expertise and dedication to advancing knowledge in these important areas of medical science and research. is listed in the reference of citation [3].

▎Relevant Citations

[1] Thadi A, Gleeson E M, Khalili M, et al. Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes[J]. Annals of Clinical and Laboratory Science, 2020,50(5):611-624. https://pubmed.ncbi.nlm.nih.gov/33067207/

[2] Sookraj K A, Bowne W B, Adler V, et al. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide[J]. Cancer Chemotherapy and Pharmacology, 2010,66(2):325-331.DOI:10.1007/s00280-009-1166-7.

[3] Sarafraz-Yazdi E, Mumin S, Cheung D, et al. 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[J]. Biomedicines, 2022,10(5).DOI:10.3390/biomedicines10050945.

[4] Darban S A, Badiee A, Jaafari M R. PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells[J]. Nanomedicine, 2017,12(12):1475-1490.DOI:10.2217/nnm-2017-0069.

[5] Alagkiozidis I, Gorelick C, Shah T, et al. Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer (Retraction of Vol 47, Pg 271, 2017)[J]. Annals of Clinical and Laboratory Science, 2017,47(4). https://pubmed.ncbi.nlm.nih.gov/28667027/

[6] Sarafraz-Yazdi E, Gorelick C, Wagreich A R, et al. Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer[J]. Annals of Clinical and Laboratory Science, 2015,45(6):650-658. https://pubmed.ncbi.nlm.nih.gov/26663795/

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