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Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization
- Source :
- Cancers, Volume 12, Issue 4, Cancers, Vol 12, Iss 864, p 864 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- 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&rsquo<br />s biological activities. The increasing affordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound&rsquo<br />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.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell cycle checkpoint
Drug design
Computational biology
lcsh:RC254-282
RNASeq
Article
03 medical and health sciences
0302 clinical medicine
Microtubule
medicine
Regulation of gene expression
Chemistry
Biological activity
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
tubulin
Oncology
Mechanism of action
Drug development
cell cycle arrest
030220 oncology & carcinogenesis
Topoisomerase-II Inhibitor
medicine.symptom
microtubule
Subjects
Details
- ISSN :
- 20726694
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....120b2eddaa7435fca980298ec780d385