Isoquinolinamine FX-9 Exhibits Anti-Mitotic Activity in Human and Canine Prostate Carcinoma Cell Lines

• Published in: International journal of molecular sciences 2019-11, Vol.20 (22), p.5567
• Main Authors: Schille, Jan Torben, Nolte, Ingo, Packeiser, Eva-Maria, Wiesner, Laura, Hein, Jens Ingo, Weiner, Franziska, Wu, Xiao-Feng, Beller, Matthias, Junghanss, Christian, Murua Escobar, Hugo
• Format: Article
• Language: English
• Subjects: Androgens; Animals; anti-mitotic; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Cell cycle; Cell division; Cell growth; cell line; Cell viability; chemotherapy; Cytokinesis; dog; Dog Diseases - drug therapy; Dog Diseases - metabolism; Dog Diseases - pathology; Dogs; human; Humans; isoquinolinamine; Isoquinolines - chemistry; Isoquinolines - pharmacology; Male; Metastases; Metastasis; Mitosis - drug effects; Morphology; PC-3 Cells; Polyploidy; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - veterinary; Tumor cell lines; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225567

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-9's 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.