Journal article
Pre-Clinical Study Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Neuroblastoma
Cancers, Vol.14(8), p.1952
04/13/2022
DOI: 10.3390/cancers14081952
PMCID: PMC9026148
PMID: 35454859
Abstract
Protein phosphatase 2A (PP2A) functions as an inhibitor of cancer cell proliferation, and its tumor suppressor function is attenuated in many cancers. Previous studies utilized FTY720, an immunomodulating compound known to activate PP2A, and demonstrated a decrease in the malignant phenotype in neuroblastoma. We wished to investigate the effects of two novel PP2A activators, ATUX-792 (792) and DBK-1154 (1154).
Long-term passage neuroblastoma cell lines and human neuroblastoma patient-derived xenograft (PDX) cells were used. Cells were treated with 792 or 1154, and viability, proliferation, and motility were examined. The effect on tumor growth was investigated using a murine flank tumor model.
Treatment with 792 or 1154 resulted in PP2A activation, decreased cell survival, proliferation, and motility in neuroblastoma cells. Immunoblotting revealed a decrease in MYCN protein expression with increasing concentrations of 792 and 1154. Treatment with 792 led to tumor necrosis and decreased tumor growth in vivo.
PP2A activation with 792 or 1154 decreased survival, proliferation, and motility of neuroblastoma in vitro and tumor growth in vivo. Both compounds resulted in decreased expression of the oncogenic protein MYCN. These findings indicate a potential therapeutic role for these novel PP2A activators in neuroblastoma.
Details
- Title: Subtitle
- Pre-Clinical Study Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Neuroblastoma
- Creators
- Laura V Bownes - University of Alabama at BirminghamRaoud Marayati - University of Alabama at BirminghamColin H Quinn - University of Alabama at BirminghamAndee M Beierle - University of Alabama at BirminghamSara C Hutchins - University of Alabama at BirminghamJanet R Julson - University of Alabama at BirminghamMichael H Erwin - University of Alabama at BirminghamJerry E Stewart - University of Alabama at BirminghamElizabeth Mroczek-Musulman - Children's of AlabamaMichael Ohlmeyer - Princeton Satellite SystemsJamie M Aye - University of Alabama at BirminghamKarina J Yoon - University of Alabama at BirminghamElizabeth A Beierle - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.14(8), p.1952
- Publisher
- MDPI; BASEL
- DOI
- 10.3390/cancers14081952
- PMID
- 35454859
- PMCID
- PMC9026148
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Grant note
- N/A / Lombardi Cancer Research Fund/Starr Children's Fund P30 CA013148 / NIH HHS P30 AI27667 / NIH HHS N/A / Elaine Roberts Foundation P30 AR048311 / NIH HHS 5T32GM008361 / NIH HHS T32 CA229102 / NIH HHS N/A / Open Hearts Overflowing Hands N/A / Sid Strong Foundation P30 CA013148 / NCI NIH HHS
- Language
- English
- Date published
- 04/13/2022
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984701646502771
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