In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors

Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.

Isolamento, purificação e caracterização da peroxidase de yacon (Smallanthus sonchifolius)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inibidores de etileno na pós-colheita de Lisianthus

Pós-graduação em Agronomia (Horticultura) - FCA

Cross linked Poly (4-Vinylpyridine-Ethylene Glycol Dimethacrylate) Used for Preconcentration of Cd(II) and its Determination by Flow Injection Flame Atomic Absorption Spectrometry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Erythrina mulungu Alkaloids Are Potent Inhibitors of Neuronal Nicotinic Receptor Currents in Mammalian Cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Density, Refractive Index, Apparent Specific Volume, and Electrical Conductivity of Aqueous Solutions of Poly(ethylene glycol) 1500 at Different Temperatures

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparison of selective and non selective cyclo-oxygenase 2 inhibitors in experimental colitis exacerbation: role of leukotriene B4 and superoxide dismutase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development of a method for sampling and determination of corrosion inhibitors in modified atmospheres

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Novel bioassay for the discovery of inhibitors of the 2-C-Methyl-D-erythritol 4-Phosphate (MEP) and terpenoid pathways leading to carotenoid biosynthesis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Water activity of aqueous solutions of ethylene oxide-propylene oxide block copolymers and maltodextrins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental and Theoretical Studies of Volatile Corrosion Inhibitors Adsorption on Zinc Electrode

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rapid synthesis of Mn3O4 powder from pyro-synthesis of ethylene glycol-metal nitrate precursor assisted by nitric acid

The rapid synthesis of Mn3O4 powders by a two-step process of pyro-synthesis of ethylene glycol-metal nitrate precursor assisted by nitric acid is reported. A new strategy that accelerates the synthesis and allows obtaining highly pure crystalline Mn3O4 is discussed. The structural and morphological characteristics of the Mn3O4 powders are presented and discussed. The mechanism of formation of the Mn3O4 is also discussed. In comparison with other synthesis methods, the present method shows that the proposed route of synthesis has the main advantage of high production of the powder material in a very short time.