Targeting Membrane HDM-2 by PNC-27 Induces Necrosis in Leukemia Cells But Not in Normal Hematopoietic Cells.
Antineoplastic Agents
/ metabolism
Cell Line, Tumor
Cell Membrane
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Humans
L-Lactate Dehydrogenase
/ metabolism
Leukemia, Myeloid
/ metabolism
Necrosis
Proto-Oncogene Proteins c-mdm2
/ metabolism
Tumor Suppressor Protein p53
/ metabolism
Cancer cell membrane
HDM-2
PNC-27
leukemia
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
31
05
2020
revised:
18
06
2020
accepted:
20
06
2020
entrez:
4
9
2020
pubmed:
4
9
2020
medline:
22
9
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32878773
pii: 40/9/4857
doi: 10.21873/anticanres.14488
doi:
Substances chimiques
Antineoplastic Agents
0
PNC-27
0
Tumor Suppressor Protein p53
0
L-Lactate Dehydrogenase
EC 1.1.1.27
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4857-4867Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.