Repozytorium publikacji - Politechnika Gdańska

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.

Autorzy

• dr Jarosław Króliczewski,,
• Sylwia Bartoszewska,
• Magdalena Dudkowska,
• Dorota Janiszewska,
• Agnieszka Biernatowska,
• David Crossman,
• Karol Krzymiński,
• Małgorzata Wysocka,
• Anna Romanowska,
• prof. dr hab. inż. Maciej Bagiński link otwiera się w nowej karcie ,
• Michal Markuszewski link otwiera się w nowej karcie ,
• Renata J. Ochocka,
• James F. Collawn,
• Aleksander F. Sikorski,
• Ewa Sikora,
• Rafal Bartoszewski