title: Fate of primary cells at the G₁/S boundary after polo-like kinase 1 inhibition by SBE13.
abstract: Human polo-like kinase 1 (Plk1), a key regulator of mitosis, is over-expressed in various human tumors. It is a negative prognostic factor for cancer patients and a measure for the aggressiveness of a tumor. Thus, targeting Plk1 might be a promising approach for cancer therapy. Plk1 inhibitors represent attractive tools for cancer research and for the mechanistic investigation of checkpoint control. Here, we show the impact of Plk1 inhibition on cell cycle regulation in primary cells. After treatment with SBE13 the G₁//S checkpoint was intact, indicated by reduced pRb, resulting in slower cell cycle progression but overall cell proliferation was not significantly impaired. Thus, we provide strong evidence that SBE13 leaves checkpoint control in primary cells unaffected making it a remarkable future anti-cancer therapeutic.
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, Goethe-University, Frankfurt, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Keppner
authors.forename: Ewgenij
authors.initials: E
authors.lastname: Proschak
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Birgit
authors.initials: B
authors.lastname: Spänkuch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D034741:RNA, Small Interfering; D016196:S Phase / Q000187:drug effects; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C549033:SBE13 compound; C413374:p27 antigen