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

doi:10.21873/anticanres.14488

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 journal › Article › peer-review

3 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 language	English
Pages (from-to)	4857-4867
Number of pages	11
Journal	Anticancer Research
Volume	40
Issue number	9
DOIs	https://doi.org/10.21873/anticanres.14488
State	Published - 1 Sep 2020
Externally published	Yes

Keywords

Cancer cell membrane
HDM-2
Leukemia
PNC-27

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.14488

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Thadi, A., Lewis, L., Goldstein, E., Aggarwal, A., Khalili, M., Steele, L., Polyak, B., Seydafkan, S., Bluth, M. H., Ward, K. A., Styler, M., Campbell, P. M., Pincus, M. R., & Bowne, W. B. (2020). Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells Βut Not in Normal Hematopoietic Cells. Anticancer Research, 40(9), 4857-4867. https://doi.org/10.21873/anticanres.14488

@article{59b3512da7db498396700d76fdd86ecd,

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

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.",

keywords = "Cancer cell membrane, HDM-2, Leukemia, PNC-27",

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

year = "2020",

month = sep,

day = "1",

doi = "10.21873/anticanres.14488",

language = "English",

volume = "40",

pages = "4857--4867",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "9",

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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 2020, 'Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells Βut Not in Normal Hematopoietic Cells', Anticancer Research, vol. 40, no. 9, pp. 4857-4867. https://doi.org/10.21873/anticanres.14488

TY - JOUR

T1 - Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells Βut Not in Normal Hematopoietic Cells

AU - Thadi, Anusha

AU - Lewis, Lauren

AU - Goldstein, Eve

AU - Aggarwal, Anshu

AU - Khalili, Marian

AU - Steele, Lindsay

AU - Polyak, Boris

AU - Seydafkan, Shabnam

AU - Bluth, Martin H.

AU - Ward, Kristine A.

AU - Styler, Michael

AU - Campbell, Paul M.

AU - Pincus, Matthew R.

AU - Bowne, Wilbur B.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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.

AB - 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.

KW - Cancer cell membrane

KW - HDM-2

KW - Leukemia

KW - PNC-27

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U2 - 10.21873/anticanres.14488

DO - 10.21873/anticanres.14488

M3 - Article

C2 - 32878773

AN - SCOPUS:85090260898

SN - 0250-7005

VL - 40

SP - 4857

EP - 4867

JO - Anticancer Research

JF - Anticancer Research

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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