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In Vitro Assessment of the Role of p53 on Chemotherapy Treatments in Neuroblastoma Cell Lines
Article

BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10

1
Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
2
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan
3
Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 11529, Taiwan
4
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10017, Taiwan
5
Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
6
Center for Computational and Systems Biology, National Taiwan University, Taipei 10617, Taiwan
*
Authors to whom correspondence should be addressed.
Authors contributed equally to this work and share first authorship.
Academic Editors: Saurabh Agarwal and Giorgio Cozza
Pharmaceuticals 2022, 15(1), 37; https://doi.org/10.3390/ph15010037
Received: 23 October 2021 / Revised: 23 December 2021 / Accepted: 23 December 2021 / Published: 28 December 2021
(This article belongs to the Special Issue Neuroblastoma Pathogenesis and Therapy)
DNA replication is initiated with the recognition of the starting point of multiple replication forks by the origin recognition complex and activation of the minichromosome maintenance complex 10 (MCM10). Subsequently, DNA helicase, consisting of the MCM protein subunits MCM2-7, unwinds double-stranded DNA and DNA synthesis begins. In previous studies, replication factors have been used as clinical targets in cancer therapy. The results showed that MCM2 could be a proliferation marker for numerous types of malignant cancer. We analyzed samples obtained from patients with neuroblastoma, revealing that higher levels of MCM2 and MCM10 mRNA were associated with poor survival rate. Furthermore, we combined the results of the perturbation-induced reversal effects on the expression levels of MCM2 and MCM10 and the sensitivity correlation between perturbations and MCM2 and MCM10 from the Cancer Therapeutics Response Portal database. Small molecule BI-2536, a polo-like kinase 1 (PLK-1) inhibitor, is a candidate for the inhibition of MCM2 and MCM10 expression. To test this hypothesis, we treated neuroblastoma cells with BI-2536. The results showed that the drug decreased cell viability and reduced the expression levels of MCM2 and MCM10. Functional analysis further revealed enrichments of gene sets involved in mitochondria, cell cycle, and DNA replication for BI-2536-perturbed transcriptome. We used cellular assays to demonstrate that BI-2536 promoted mitochondria fusion, G2/M arrest, and apoptosis. In summary, our findings provide a new strategy for neuroblastoma therapy with BI-2536. View Full-Text
Keywords: minichromosome maintenance complex 2 and 10; BI-2536; neuroblastoma; mitochondria fusion; cell death minichromosome maintenance complex 2 and 10; BI-2536; neuroblastoma; mitochondria fusion; cell death
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MDPI and ACS Style

Hsieh, C.-H.; Yeh, H.-N.; Huang, C.-T.; Wang, W.-H.; Hsu, W.-M.; Huang, H.-C.; Juan, H.-F. BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10. Pharmaceuticals 2022, 15, 37. https://doi.org/10.3390/ph15010037

AMA Style

Hsieh C-H, Yeh H-N, Huang C-T, Wang W-H, Hsu W-M, Huang H-C, Juan H-F. BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10. Pharmaceuticals. 2022; 15(1):37. https://doi.org/10.3390/ph15010037

Chicago/Turabian Style

Hsieh, Chiao-Hui, Hsiang-Ning Yeh, Chen-Tsung Huang, Wei-Hsuan Wang, Wen-Ming Hsu, Hsuan-Cheng Huang, and Hsueh-Fen Juan. 2022. "BI-2536 Promotes Neuroblastoma Cell Death via Minichromosome Maintenance Complex Components 2 and 10" Pharmaceuticals 15, no. 1: 37. https://doi.org/10.3390/ph15010037

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