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Thadi A , Lewis L , Goldstein E , Aggarwal A , Khalili M , Steele L , Polyak B , Seydafkan S , Bluth MH , Ward KA , Styler M , Campbell PM , Pincus MR , Bowne WB
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
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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.
1791-7530 Thadi, Anusha Lewis, Lauren Goldstein, Eve Aggarwal, Anshu Khalili, Marian Steele, Lindsay Polyak, Boris Seydafkan, Shabnam Bluth, Martin H Ward, Kristine A Styler, Michael Campbell, Paul M Pincus, Matthew R Bowne, Wilbur B Journal Article Greece Anticancer Res. 2020 Sep;40(9):4857-4867. doi: 10.21873/anticanres.14488.