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, 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.
Subject(s)
Antineoplastic Agents/pharmacology , Leukemia, Myeloid/pathology , Proto-Oncogene Proteins c-mdm2/metabolism , Tumor Suppressor Protein p53/pharmacology , Antineoplastic Agents/metabolism , 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 , Necrosis , Tumor Suppressor Protein p53/metabolismABSTRACT
The aim of this mental health promotion initiative was to evaluate the effectiveness of a universally delivered group behavioral family intervention (BFI) in preventing behavior problems in children. This study investigates the transferability of an efficacious clinical program to a universal prevention intervention delivered through child and community health services targeting parents of preschoolers within a metropolitan health region. A quasi-experimental two-group (BFI, n = 804 vs. Comparison group, n = 806) longitudinal design followed preschool aged children and their parents over a 2-year period. BFI was associated with significant reductions in parent- reported levels of dysfunctional parenting and parent-reported levels of child behavior problems. Effect sizes on child behavior problems ranged from large (.83) to moderate (.47). Positive and significant effects were also observed in parent mental health, marital adjustment, and levels of child rearing conflict. Findings are discussed with respect to their implication for significant population reductions in child behavior problems as well as the pragmatic challenges for prevention science in encouraging both the evaluation and uptake of preventive initiatives in real world settings.
