PDA Indolylmaleimides Induce Anti-Tumor Effects in Prostate Carcinoma Cell Lines Through Mitotic Death

Jan Torben Schille, Ingo Nolte, Julia Beck, Daria Jilani, Catrin Roolf, Anahit Pews-Davtyan, Arndt Rolfs, Larissa Henze, Matthias Beller, Bertram Brenig, Christian Junghanss, Ekkehard Schütz, Hugo Murua Escobar

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article number558135
JournalFrontiers in Veterinary Science
Volume7
DOIs
StatePublished - 20 Jan 2021
Externally publishedYes

Keywords

  • dog
  • human
  • mitotic death
  • mitotic slippage
  • prostate cancer
  • whole transcriptome sequencing

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