Abstract

Castrate resistant prostate cancer in men shares several characteristics with canine prostate cancer (PCa). Due to current insufficient therapies, evaluating novel therapeutic agents for late-stage PCa is of considerable interest for both species. PDA indolylmaleimides showed anticancer effects in several neoplastic cell lines. Herein, a comparative characterization of PDA-66 and PDA-377 mediated effects was performed in human and canine PCa cell lines, which is also the first detailed characterization of these agents on cells derived from solid tumors in general. While PDA-377 showed only weak growth inhibition on human PCa cell lines, PDA-66 inhibited proliferation and induced apoptosis in human and canine cell lines with concentrations in the low micromolar range. Morphological characterization and whole transcriptome sequencing revealed that PDA-66 induces mitotic death through its microtubule-depolymerizing ability. PDA-66 appears to be a worthwhile anti-mitotic agent for further evaluation. The similarities in cellular and molecular response observed in the cell lines of both origins form a solid basis for the use of canine PCa in vivo models to gain valuable interchangeable data to the advantage of both species.

Highlights

  • Prostate cancer (PCa) is the most common malignancy diagnosed among males in almost all western countries [1]

  • The aim of this study was to comparatively characterize the influence of PDA-66 and PDA-377 on two human prostate carcinoma cell lines, PC-3 and LNCaP, and on the canine cell line CT1258, which is the first detailed characterization of these agents on cells derived from solid tumors

  • PDA-377 incubation caused no visual effects after 5 μM treatment for 72 h, and only minor effects on the PC-3 cell line after 15 μM treatment for 24 h

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Summary

Introduction

Prostate cancer (PCa) is the most common malignancy diagnosed among males in almost all western countries [1]. PCa emerges in an androgen-dependent or androgen-independent manner with a highly heterogeneous clinical course. Localized PCa has a 5-year survival rate close to 100% due to the availability of a broad range of curative treatment options. Up to 20% of patients develops incurable and lethal metastatic castrate-resistant PCa within 5 years of follow-up. The development of novel therapeutic options for treating high-risk locally advanced PCa is needed [2,3,4,5].

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