Lapatinib-Loaded Nanocapsules Enhances Antitumoral Effect in Human Bladder Cancer Cell

Transitional cell carcinoma (TCC) represents the most frequent type of bladder cancer. Recently, studies have focused on molecular tumor classifications in order to diagnose tumor subtypes and predict future clinical behavior. Increased expression of HER1 and HER2 receptors in TTC is related to advanced stage tumors. Lapatinib is an important alternative to treat tumors that presents this phenotype due to its ability to inhibit tyrosine kinase residues associated with HER1 and HER2 receptors. This study evaluated the cytotoxicity induced by LAP-loaded nanocapsules (NC-LAP) compared to LAP in HER-positive bladder cancer cell. The cytotoxicity induced by NC-LAP was evaluated through flow cytometry, clonogenic assay and RT-PCR. NC-LAP at 5 μM reduced the cell viability and was able to induce G0/G1 cell cycle arrest with up-regulation of p21. Moreover, NC-LAP treatment presented significantly higher apoptotic rates than untreated cells and cells incubated with drug-unloaded nanocapsules (NC) and an increase in Bax/Bcl-2 ratio was observed in T24 cell line. Furthermore, clonogenic assay demonstrated that NC-LAP treatment eliminated almost all cells with clonogenic capacity. In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype

ASSOCIAÇÃO ENTRE A PRESENÇA DE UM FATOR DE 38 kDa NO PLASMA SEMINAL E A INIBIÇÃO DA MOTILIDADE ESPERMÁTICA NO JUNDIÁ Rhamdia quelen

Fatores proteicos tem sido indentificados no plasma seminal de peixes e mamíferos e, em algumas situações, associados com indicadores de qualidade espermática. Entretanto, para o jundiá (Rhamdia quelen), tais fatores como aqueles com potenciais associações ainda não foram descritos. Os objetivos deste estudo foram de identificar alguns fatores proteicos presentes no plasma seminal do jundiá e avaliar suas associações com a motilidade espermática. Através de eletroforese do tipo SDS-PAGE foram identificadas 14 bandas proteicas com peso molecular entre 217.1 e 7.1 kDa.  A motilidade espermática foi avaliada em 21 machos. Quatro bandas proteicas (81.5; 60.4; 33.6 e 25.5 kDa) foram detectadas em todas as amostras de plasma seminal analisadas. Uma banda proteica com peso molecular de 38.3 kDa foi associada com a baixa motilidade espermática no jundiá (P< 0,01), uma vez que foi detectada em 91.4% das amostras com motilidade menor que 80%. Estes resultados sugerem que esta banda proteica seminal associada com a baixa motilidade espermática poderá ser considerada como um potencial marcador bioquímico de qualidade seminal. Palavras-chaveS: Motilidade espermática, plasma seminal, proteínas, Rhamdia quelen, SDS-PAGE

Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important intermediates applied in organic synthesis. Our objective was to investigate the effect and the underlying cell death mechanisms of AZT and its derivatives, in human breast cancer cell lines. The inhibitory effect of AZT and derivatives (1072, 1073, and 1079) was determined by MTT assay (0.1, 1, 10, 50, and 100 μM for concentrations and times 4, 24, 48, and 72 h) and Live/Dead in tumor cell lines MCF-7, MDA-MB 231 and also in non-tumor cell line CHO. Gene expression profiles related to apoptosis were investigated by qRT-PCR and induction of apoptosis was investigated by flow cytometry. MTT and Live/Dead assays showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 50 and 100 μM in tumor cell lines MCF-7 and MDA-MB 231 while the commercial AZT presented a low antitumoral potential in all strains tested. In flow cytometry analysis we demonstrated that derivatives of AZT induced apoptosis, with an increase in both initial and late stages in both tumor cell lines evaluated, especially in MDA-MB 231. Our data show that the AZT derivative 1072 increased the expression of transcripts of the genes caspase 3 and 8 in MDA-MB 231 cell line when compared to control, suggesting that the extrinsic pathway of apoptosis was activated. In conclusion, derivatives of AZT, especially 1072, induce cytotoxicity in vitro in the triple negative breast cancer cell line through activation of the extrinsic pathway of apoptosis. These compounds containing selenium in its formulation are potential therapeutic agents for breast cancer

Cytotoxic Activity of Fatty Acids From Antarctic Macroalgae on the Growth of Human Breast Cancer Cells

Macroalgae are a natural source of clinically relevant molecules such as polyunsaturated and monounsaturated fatty acids. The Antarctic environment, due to its cold climate, leads to high production of these bioactive molecules. Adenocystis utricularis, Curdiea racovitzae, and Georgiella confluens from three distinct islands in the Antarctic Peninsula were collected and analyzed for their fatty acid content by gas chromatography flame ionization detection. Results revealed that the algal extracts consisted of 22 fatty acids, of which 9 were saturated, 4 were monounsaturated, and 9 were polyunsaturated (PUFA). In addition, fucosterol was identified within the lipidic extracts. The cytotoxic activity of these fatty acids was evaluated in human breast cancer cell lines MCF-7 and MDA-MB-231. The most notable result was the effect of PUFA on the growth inhibition of cancer cells ranging from 61.04 to 69.78% in comparison to control cells. Significant cytotoxic activity of fatty acids from A. utricularis was observed at 48 h, resulting in an inhibition of growth of more than 50% for breast cancer cells at a concentration of 100 μg/mL. A cell viability assay showed that the fatty acids from A. utricularis significantly reduced cell viability (68.7% in MCF-7 and 89% in MDA-MB-231 after 72 h of exposure). At the same time, DAPI staining demonstrated chromatin condensation, and apoptotic bodies formed in cells that were cultured with fatty acids from A. utricularis. These data indicate that fatty acids from Antarctic macroalgae have the potential to reduce the proliferation of and induce apoptosis in breast cancer cells

Auxotrophic <i>Mycobacterium bovis</i> BCG: Updates and Perspectives

Mycobacterium bovis BCG has been used for a century as the only licensed vaccine against tuberculosis. Owing to its strong adjuvant properties, BCG has also been employed as an oncological immunotherapeutic as well as a live vaccine vector against other pathogens. However, BCG vaccination has limited efficacy in protecting against adult forms of tuberculosis (TB), raises concerns about its safety in immunocompromised populations, compromises the diagnosis of TB through the tuberculin test and lacks predictability for successful antigen expression and immune responses to heterologous antigens. Together, these factors propelled the construction and evaluation of auxotrophic BCG strains. Auxotrophs of BCG have been developed from mutations in the genes required for their growth using different approaches and have shown the potential to provide a model to study M. tuberculosis, a more stable, safe, and effective alternative to BCG and a vector for the development of recombinant live vaccines, especially against HIV infection. In this review, we provide an overview of the strategies for developing and using the auxotrophic BCG strains in different scenarios