PNC-27 Dosage

PNC-27 is a peptide that contains p53 protein residues and binds to HDM-2 receptors, which are synthesized in higher levels in the nucleus and membrane of tumor cells. Its main effect is necrosis and lysis of these cells, which is why this peptide may help in treating various forms of cancer. Scientific studies have determined that this potential can be used in treating acute myeloid leukemia, colon adenocarcinoma, epithelial ovarian cancer, and many other forms. Scientists believe that, in combination with radiotherapy, chemotherapy, or cytostatics, it can provide improvements in the size and spread of tumors, as well as prevent the likelihood of metastases to nearby or distant organs. These abilities of the peptide resulted in a better general condition of the patient and a greater chance of survival.

Dosing Chart

About the Peptide

PNC-27 is a peptide molecule that contains amino acid residues of the p53 protein. It binds to HDM-2 receptors, which are highly expressed on the cell membrane in tumors. Based on research, it was determined that these receptors are present in the cellular components of both solid and non-solid tumors, which increases the therapeutic potential of the peptide. After binding, the peptide induces cell death in both its forms (apoptosis and necrosis). As a result, the tumor can be reduced, limited, and, most importantly, prevented from spreading to surrounding healthy tissues (metastasis).

One of the first forms of malignancy where the PNC-27 potential was discovered was acute myeloid leukemia. It is a form of cancer that develops suddenly and progresses extremely quickly, so it is necessary to start treatment immediately. The disease affects the bone marrow, which is responsible for producing blood elements. Their further synthesis is disrupted and cannot occur regularly, resulting in symptoms such as frequent breakdowns, spontaneous bruising, weakness, and nighttime fever. It is believed that after entering the body and binding to peptide receptors, the peptide can cause the formation of pores on the cell surface, leading to cell death. These properties are primarily due to the p53 amino acid residue in the peptide, which is known as a tumor suppressor. Scientists assume that this therapy may be beneficial during exacerbations (recurrences of the disease) when resistance to treatment with previous therapies typically occurs.

According to scientific research, it has been determined that PNC-27 can exert the same effect on epithelial ovarian cancer cells in humans. Cystadenocarcinoma is a severe form of the disease where the impact of the peptide has been most studied. Diagnosis occurs as a result of cyst formation, progresses rapidly, and can spread to other organs. It is proven that PNC-27 exhibits cytotoxic activity against this type of cell, leading to necrosis, which in turn results in a decrease in tumor size and symptom relief.

It has been found that the peptide can achieve similar effects in treating colorectal cancer. This is a severe form of malignancy that occurs relatively often in young and elderly populations but more often in men. Using similar mechanisms of action, binding to receptors on the cell surface and killing primarily CD44+ cells. As a result, cell lysis and necrosis of tumor tissue occur. The patient experiences an improvement in his overall condition, and, most importantly, the risk of cancer spreading (metastasis) is significantly reduced. Symptoms of vague diarrhea, abdominal cramps, visible blood and mucus in the stool decrease over time, which may result in complete healing. Treatment with the PNC-27 peptide can be combined with chemotherapy, radiotherapy, or cytostatics or used alone.

List of Uses

Impact on the Development of Acute Lymphoid Leukemia

Acute myeloid leukemia is a form of malignancy that primarily attacks the bone marrow. It is located in the trabeculae of the spongy bone and is designed to produce blood cells (leukocytes, erythrocytes, lymphocytes, and other forms that arise from them). This form of cancer progresses very quickly and spreads through the bloodstream to other organs. Because of these characteristics, it is necessary to react as swiftly and effectively as possible to save a life. When abnormal growth of myeloid cells occurs in the bone marrow, the normal production of blood elements is harrowing. This results in a decrease in immunity, loss of general well-being, frequent bleeding, bruising, night sweats, and increased body temperature. In addition, patients are often anemic and pale.

After the patient ingests PNC-27, it immediately goes directly to the HDM-2 receptors located on the cell membrane or nucleus of the malignant cell. The next step is the automatic creation of pores, which destabilize the cell, allowing for increased water penetration, ultimately leading to cell bursting. Types of cell death include necrosis (caused by external factors) or apoptosis (programmed cell death that comes as an order from the brain due to information about its damage). Unlike other antitumor therapies, this peptide primarily induces necrosis. In this way, the chance of the tumor spreading through the bloodstream is reduced, and patients experience an improvement in their general condition.

Role in the Therapy of Ovarian Cystadenocarcinoma

Ovarian cystadenocarcinoma is one of the aggressive forms of ovarian cancer that most often arises from the persistence of cysts. It has a high malignant potential, which means that there is a high probability of spreading to surrounding tissue when treatment is significantly delayed and most often results in death. It most often contains cysts of various contents and is of epithelial origin. Patients usually start to experience symptoms late, including abnormal swelling of the ovaries, back pain, weight loss, or problems urinating. Treatment is usually radiotherapy or surgery. However, peptide therapy, which is much more comfortable for the patient, according to certain studies, also results in forms of cancer resistant to chemotherapy, which is a relatively common case.

PNC-27 has similar mechanisms of action as in leukemia. The peptide binds to SKOV3-luc-D3 cells and most often causes the cessation of their proliferation. The expected result of the therapy is a reduction in the size and volume of the tumor, as well as a decrease in the proliferation and metastatic potential. As a result of combined or individual therapy, patients experience an improvement in their condition and a reduction in symptoms. These effects have been confirmed in the results of numerous scientific studies and research.

Influence on the Development of Colorectal Cancer

Colon cancer is a type of malignancy that manifests itself with straining in the stool, severe abdominal pain, or vague diarrhea. Scientists suggest that this peptide exerts its effect primarily on cancer cells. In contrast, other healthy tissue cells remain intact, mainly because they do not have receptors for the peptide to bind to. The effect of the peptide is reflected in the reduction of cell activity, viability, and toxicity. Numerous studies have confirmed the effectiveness of the drug, showing improvements, a reduced risk of spread, and a decrease in symptoms in affected patients. In the case of this condition, peptide therapy is most often combined with radiotherapy, but unlike the therapy used so far, PNC-27 leaves minimal consequences and almost no side effects.

Dosing Calculator

Dosage always depends on the indication. The primary function of this peptide is antineoplastic activity, and its effects have been studied most in acute myeloid leukemia. In this case, the peptide is initially administered in a dose of 100 mcg as a subcutaneous injection once daily. The region of choice is almost always the abdomen, and an insulin syringe is used. After a specific time, the dose can be increased to 200 mcg, but it must not be exceeded. It is administered in two to three weeks, depending on the patient’s general condition and the treatment plan.

Is It Safe?

If used as directed and recommended by a physician, PNC-27 is an entirely safe compound to use. The optimal dose should never be exceeded or changed independently. If used under the supervision of a physician, the peptide should not exhibit any severe side effects. Regardless of the current achievements, PNC-27 will remain a subject of research.

References:

1. 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
2. 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/
3. 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/
4. 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/
5. 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 DOI: 10.21873/anticanres.14488