title: Interference of a novel indolylmaleimide with microtubules induces mitotic arrest and apoptosis in human progenitor and cancer cells.
abstract: Indolylmaleimides display a broad spectrum of biological activity and offer great opportunity to influence several aspects of cell fate, as proliferation and differentiation. In this study we describe the effect of PDA-66, a newly synthesised indolylmaleimide, showing a strong dose dependent anti-proliferative effect on immortalised human progenitor and cancer cells. We demonstrated a highly depolymerizing effect on in vitro tubulin assembly and conclude that PDA-66 acts as microtubule destabilising agent. In addition we found that PDA-66 induces mitotic arrest of cells in the G₂/M phase of the cell cycle. Subsequently cells undergo apoptosis, indicating the major mechanism of the anti-proliferative effect. To prove a potential anti-cancer activity of PDA-66 we examined the effect of PDA-66 on human SH-SY5Y neuroblastoma and A-459 lung cancer cells, showing a significant reduction in cancer cell proliferation in a dose dependent manner. Thus PDA-66 is a new anti-mitotic compound with an indole-core with the potential to be used for cancer therapy.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Center for Mental Health, University of Rostock, Germany. christian.eisenloeffel@uni-rostock.de
authors.forename: Christian
authors.initials: C
authors.lastname: Eisenlöffel
authors.forename: Anne-Caroline
authors.initials: AC
authors.lastname: Schmöle
authors.forename: Anahit
authors.initials: A
authors.lastname: Pews-Davtyan
authors.forename: Anne
authors.initials: A
authors.lastname: Brennführer
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kuznetsov
authors.forename: Rayk
authors.initials: R
authors.lastname: Hübner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Frech
authors.forename: Catrin
authors.initials: C
authors.lastname: Schult
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanss
authors.forename: Matthias
authors.initials: M
authors.lastname: Beller
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.forename: Moritz J
authors.initials: MJ
authors.lastname: Frech
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism
chemical_list: D007211:Indoles; D008301:Maleimides; C579844:PDA-66; D014404:Tubulin