Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells
| Autor: | Matthew R. Pincus, Kristine A Ward, Lauren Lewis, Eve Goldstein, Wilbur B. Bowne, Marian Khalili, Boris Polyak, Martin H. Bluth, Anusha Thadi, Anshu Aggarwal, Shabnam Seydafkan, Michael Styler, Lindsay Steele, Paul M Campbell |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Acute promyelocytic leukemia
Cancer Research Cell Survival HL60 Cell Antineoplastic Agents Necrosis chemistry.chemical_compound Cell Line Tumor medicine Humans Acute monocytic leukemia Viability assay Dose-Response Relationship Drug L-Lactate Dehydrogenase Chemistry Cell Membrane Proto-Oncogene Proteins c-mdm2 General Medicine medicine.disease Leukemia medicine.anatomical_structure Oncology Leukemia Myeloid Cancer cell Acute myelomonocytic leukemia Cancer research Tumor Suppressor Protein p53 |
| Zdroj: | Anticancer Research. 40:4857-4867 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.14488 |
| Popis: | Background/aim Anticancer peptide PNC-27 binds to HDM-2 protein on cancer cell membranes inducing the formation of cytotoxic transmembrane pores. Herein, we investigated HDM-2 membrane expression and the effect of PNC-27 treatment on human non-stem cell acute myelogenous leukemia cell lines: U937, acute monocytic leukemia; OCI-AML3, acute myelomonocytic leukemia and HL60, acute promyelocytic leukemia. Materials and methods We measured cell surface membrane expression of HDM-2 using flow cytometry. Cell viability was assessed using MTT assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers annexin V and caspase-3. Results HDM-2 is expressed at high levels in membranes of U937, OCI-AML3 and HL-60 cells. PNC-27 can bind to membrane HDM-2 to induce cell necrosis and LDH release within 4 h. Conclusion Targeting membrane HDM-2 can be a potential strategy to treat leukemia. PNC-27 targeting membrane HDM-2 demonstrated significant anti-leukemia activity in a variety of leukemic cell lines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|