Journal article
The Effects of Protein Phosphatase 2A Activation with Novel Tricyclic Sulfonamides on Hepatoblastoma
Journal of pediatric surgery, Vol.58(6), pp.1145-1154
06/01/2023
DOI: 10.1016/j.jpedsurg.2023.02.017
PMCID: PMC10198925
PMID: 36907775
Abstract
Background: The tumor suppressor, protein phosphatase 2A (PP2A), is downregulated in hepato-blastoma. We aimed to examine the effects of two novel compounds of the tricyclic sulfonamide class, ATUX-3364 (3364) and ATUX-8385 (8385), designed to activate PP2A without causing immunosup-pression, on human hepatoblastoma.Methods: An established human hepatoblastoma cell line, HuH6, and a human hepatoblastoma patient -derived xenograft, COA67, were treated with increasing doses of 3364 or 8385, and viability, prolifera-tion, cell cycle and motility were investigated. Cancer cell stemness was evaluated by real-time PCR and tumorsphere forming ability. Effects on tumor growth were examined using a murine model.Results: Treatment with 3364 or 8385 significantly decreased viability, proliferation, cell cycle pro-gression and motility in HuH6 and COA67 cells. Both compounds significantly decreased stemness as demonstrated by decreased abundance of OCT4, NANOG, and SOX2 mRNA. The ability of COA67 to form tumorspheres, another sign of cancer cell stemness, was significantly diminished by 3364 and 8385. Treatment with 3364 resulted in decreased tumor growth in vivo.Conclusion: Novel PP2A activators, 3364 and 8385, decreased hepatoblastoma proliferation, viability, and cancer cell stemness in vitro. Animals treated with 3364 had decreased tumor growth. These data provide evidence for further investigation of PP2A activating compounds as hepatoblastoma therapeutics.(c) 2023 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- The Effects of Protein Phosphatase 2A Activation with Novel Tricyclic Sulfonamides on Hepatoblastoma
- Creators
- Laura V Bownes - University of AlabamaJanet R. Julson - University of Alabama at BirminghamColin H. Quinn - University of Alabama at BirminghamSara Claire Hutchins - University of Alabama at BirminghamMichael H. Erwin - University of Alabama at BirminghamHooper R. Markert - University of Alabama at BirminghamJerry E. Stewart - University of Alabama at BirminghamElizabeth Mroczek-Musulman - Childrens Alabama, Dept Pathol, Birmingham, AL 35233 USAJamie Aye - University of Alabama at BirminghamKarina J. Yoon - University of Alabama at BirminghamMichael Ohlmeyer - Princeton Satellite Systems (United States)Elizabeth A. Beierle - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric surgery, Vol.58(6), pp.1145-1154
- DOI
- 10.1016/j.jpedsurg.2023.02.017
- PMID
- 36907775
- PMCID
- PMC10198925
- NLM abbreviation
- J Pediatr Surg
- ISSN
- 0022-3468
- eISSN
- 1531-5037
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- Sid Strong Foundation Destiny StrongER Foundation Starr Fund-Vince Lombardi Cancer Foundation Elaine Roberts Foundation T32 CA229102; 5T32GM008361; P30 AR048311; P30 AI027767; CA013148 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Dixon grant Rally Foundation for Childhood Cancer Research Open Hands Overflowing Hearts Kaul Pediatric Research Foundation
- Language
- English
- Date published
- 06/01/2023
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984701553502771
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