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

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

Abstrakt

Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often dicult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing aordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse eects 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.

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Wersja publikacji
Accepted albo Published Version
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Creative Commons: CC-BY otwiera się w nowej karcie

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Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
Cancers nr 12,
ISSN: 2072-6694
Język:
angielski
Rok wydania:
2020
Opis bibliograficzny:
Króliczewski, J., Bartoszewska S., Dudkowska M., Janiszewska D., Biernatowska A., Crossman D., Krzymiński K., Wysocka m., Romanowska A., Bagiński M., Markuszewski M., Ochocka R., Collawn J., Sikorski A., Sikora E., Bartoszewski R.: Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization// Cancers -Vol. 12,iss. 4 (2020), s.864-
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.3390/cancers12040864
Źródła finansowania:
Weryfikacja:
Politechnika Gdańska

wyświetlono 129 razy

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