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

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.Univ São Paulo, Dept Genet, Fac Med Ribeirao Preto, São Paulo, BrazilUniv São Paulo, Div Pediat Oncol, Dept Pediat, Fac Med Ribeirao Preto, São Paulo, BrazilUniv São Paulo, Lab Pediat, Hosp Clin, Fac Med Ribeirao Preto, BR-14048900 Ribeirao Preto, SP, BrazilUniv São Paulo, Dept Biol, Fac Philosophy Sci & Letters Ribeirao Preto, São Paulo, BrazilWeb of Scienc