title: Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells.
abstract: Cervical adenocarcinoma is one of the most common gynecological malignancies. Despite the improvements in multimodality treatment, advanced disease is still associated with a significantly poor prognosis making the search for more effective therapeutic agents imperative. BI 2536, an unambiguous inhibitor of Polo-like kinase 1 (PLK1), has shown anticancer activity in a variety of tumor cell types. Herein, we present more evidence of the antiproliferative effects of this drug on HeLa cells. Nanomolar concentrations (10-100 nmol/l) of the drug significantly decreased cell proliferation and clonogenic capacity. Our results also demonstrate that inhibition of PLK1 promoted G2/M arrest and resulted in a dramatic increase in the mitotic index after 24 h of treatment. Apoptosis onset was evinced by the accumulation of a sub-G1 population as well as by a significant increase in caspase-3 activity at longer periods of exposure. Taken together, our results reinforce the prospect of directing against PLK1 as a potential therapeutic target to be evaluated in different preclinical models for cervical carcinoma.
authors.affiliation: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Pezuk
authors.forename: María Sol
authors.initials: MS
authors.lastname: Brassesco
authors.forename: Jaqueline C
authors.initials: JC
authors.lastname: Oliveira
authors.forename: Andressa G
authors.initials: AG
authors.lastname: Morales
authors.forename: Ana P
authors.initials: AP
authors.lastname: Montaldi
authors.forename: Elza T
authors.initials: ET
authors.lastname: Sakamoto-Hojo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Scrideli
authors.forename: Luiz G
authors.initials: LG
authors.lastname: Tone
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011621:Pteridines / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D000097869:Polo-Like Kinase 1; C518477:BI 2536
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