Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells

Anticancer Res. 2020 Sep;40(9):4857-4867. doi: 10.21873/anticanres.14488.


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.

Keywords: Cancer cell membrane; HDM-2; PNC-27; leukemia.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology*
  • Necrosis
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / pharmacology*


  • Antineoplastic Agents
  • PNC-27
  • Tumor Suppressor Protein p53
  • L-Lactate Dehydrogenase
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2