Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells

Clin Exp Med. 2013 Feb;13(1):75-80. doi: 10.1007/s10238-011-0166-1. Epub 2011 Nov 12.

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.

MeSH terms

  • Antineoplastic Agents / metabolism*
  • Apoptosis
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Proliferation / drug effects*
  • Epithelial Cells / drug effects*
  • Female
  • HeLa Cells
  • Humans
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Pteridines / metabolism*

Substances

  • Antineoplastic Agents
  • BI 2536
  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Pteridines
  • Protein Serine-Threonine Kinases