Isoquinolinamine fx-9 exhibits anti-mitotic activity in human and canine prostate carcinoma cell lines

Jan Torben Schille, Ingo Nolte, Eva Maria Packeiser, Laura Wiesner, Jens Ingo Hein, Franziska Weiner, Xiao Feng Wu, Matthias Beller, Christian Junghanss, Hugo Murua Escobar

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Current therapies are insufficient for metastatic prostate cancer (PCa) in men and dogs. As human castrate-resistant PCa shares several characteristics with the canine disease, comparative evaluation of novel therapeutic agents is of considerable value for both species. Novel isoquinolinamine FX-9 exhibits antiproliferative activity in acute lymphoblastic leukemia cell lines but has not been tested yet on any solid neoplasia type. In this study, FX-9s mediated effects were characterized on two human (PC-3, LNCaP) and two canine (CT1258, 0846) PCa cell lines, as well as benign solid tissue cells. FX-9 significantly inhibited cell viability and induced apoptosis with concentrations in the low micromolar range. Mediated effects were highly comparable between the PCa cell lines of both species, but less pronounced on non-malignant chondrocytes and fibroblasts. Interestingly, FX-9 exposure also leads to the formation and survival of enlarged multinucleated cells through mitotic slippage. Based on the results, FX-9 acts as an anti-mitotic agent with reduced cytotoxic activity in benign cells. The characterization of FX-9-induced effects on PCa cells provides a basis for in vivo studies with the potential of valuable transferable findings to the benefit of men and dogs.

Original languageEnglish
Article number5567
JournalInternational Journal of Molecular Sciences
Volume20
Issue number22
DOIs
StatePublished - 2 Nov 2019
Externally publishedYes

Keywords

  • Anti-mitotic
  • Cell line
  • Chemotherapy
  • Dog
  • Human
  • Isoquinolinamine
  • Prostate cancer

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