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Article

Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization

1
Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, 80-416 Gdansk, Poland
2
Department of Inorganic Chemistry, Medical University of Gdansk, 80-416 Gdansk, Poland
3
Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
4
Department of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw Poland
5
Department of Genetics, UAB Genomics Core Facility, University of Alabama at Birmingham, Birmingham, AL 35233, USA
6
Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, Poland
7
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland
8
Department of Biopharmacy and Pharmacodynamics, Medical University of Gdansk, 80-416 Gdansk, Poland
9
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
10
Research and Development Centre, Regional Specialist Hospital, 51-154, Wroclaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cancers 2020, 12(4), 864; https://doi.org/10.3390/cancers12040864
Received: 26 February 2020 / Revised: 21 March 2020 / Accepted: 31 March 2020 / Published: 2 April 2020
(This article belongs to the Collection Application of Bioinformatics in Cancers)
Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often difficult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing affordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse effects on gene regulation. Here, we used an unbiased approach in lung and colon cancer cell lines to identify the early transcriptomic signatures of C-1305 cytotoxicity that highlight the novel pathways responsible for its biological activity. Our results demonstrate that C-1305 promotes direct microtubule stabilization as a part of its mechanism of action that leads to apoptosis. Furthermore, we show that C-1305 promotes G2 cell cycle arrest by modulating gene expression. The results indicate that C-1305 is the first microtubule stabilizing agent that also is a topoisomerase II inhibitor. This study provides a novel approach and methodology for delineating the antitumor mechanisms of other putative anticancer drug candidates. View Full-Text
Keywords: microtubule; RNASeq; tubulin; cell cycle arrest microtubule; RNASeq; tubulin; cell cycle arrest
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MDPI and ACS Style

Króliczewski, J.; Bartoszewska, S.; Dudkowska, M.; Janiszewska, D.; Biernatowska, A.; Crossman, D.K.; Krzymiński, K.; Wysocka, M.; Romanowska, A.; Baginski, M.; Markuszewski, M.; Ochocka, R.J.; Collawn, J.F.; Sikorski, A.F.; Sikora, E.; Bartoszewski, R. Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization. Cancers 2020, 12, 864. https://doi.org/10.3390/cancers12040864

AMA Style

Króliczewski J, Bartoszewska S, Dudkowska M, Janiszewska D, Biernatowska A, Crossman DK, Krzymiński K, Wysocka M, Romanowska A, Baginski M, Markuszewski M, Ochocka RJ, Collawn JF, Sikorski AF, Sikora E, Bartoszewski R. Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization. Cancers. 2020; 12(4):864. https://doi.org/10.3390/cancers12040864

Chicago/Turabian Style

Króliczewski, Jarosław, Sylwia Bartoszewska, Magdalena Dudkowska, Dorota Janiszewska, Agnieszka Biernatowska, David K. Crossman, Karol Krzymiński, Małgorzata Wysocka, Anna Romanowska, Maciej Baginski, Michal Markuszewski, Renata J. Ochocka, James F. Collawn, Aleksander F. Sikorski, Ewa Sikora, and Rafal Bartoszewski. 2020. "Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization" Cancers 12, no. 4: 864. https://doi.org/10.3390/cancers12040864

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