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

Anusha Thadi, Lauren Lewis, Eve Goldstein, Anshu Aggarwal, Marian Khalili, Lindsay Steele, Boris Polyak, Shabnam Seydafkan, Martin H. Bluth, Kristine A. Ward, Michael Styler, Paul M. Campbell, Matthew R. Pincus, Wilbur B. Bowne

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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, OCIAML3 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.

Original languageEnglish
Pages (from-to)4857-4867
Number of pages11
JournalAnticancer Research
Volume40
Issue number9
DOIs
StatePublished - Sep 2020
Externally publishedYes

Keywords

  • Cancer cell membrane
  • HDM-2
  • Leukemia
  • PNC-27

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