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.

Eficiência de herbicidas inibidores da ALS e PROTOX sob condições de déficit hídrico no comportamento bioquímico de plantas daninhas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Participação do endotélio e das espécies reativas de oxigênio no efeito hipotensor e na resposta vasodilatadora do novo doador de Óxido Nítrico [Ru(terpy)(bdq)NO+]3+ (TERPY) em ratos espontaneamente hipertensos (SHR)

Pós-graduação em Ciências Fisiológicas - FOA

Efeito da apocinina na hipertensão, disfunção endotelial e hipertrofia ventricular esquerda em Ratos Espontaneamente Hipertensos (SHR)

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

Estudo da dinâmica conformacional das enzimas Chiquimato Quinase e 5-enolpiruvilchiquimato-3-Fosfato Sintase (EPSPS) de Mycobacterium tuberculosis através do monitoramento da troca isotópica hidrogênio/deutério por espectrometria de massas ESI

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

Efeito do L-Name na expressão de iNOS, MPO e na perda óssea alveolar em ratos diabéticos com periodontite experimental

Pós-graduação em Odontologia - FOAR

Efeitos do curcumin na modulação da inflamação e reabsorção óssea em dois modelos de doença periodontal em roedor

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)

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)

Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA >= 34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue. (C) 2014 Elsevier Inc. All rights reserved.

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

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

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)

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

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)