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

Process For Producing Functionalized Carbon Nanotubes Ntc-func That Have Thiol -sh Groups

A presente invenção refere-se a um processo de obtenção de nanotubos de carbono de parede simples (SWCNT), duplas (DWCNT) ou múltiplas (MWCNT) funcionalizados através da geração de carbânions e aplicação de enxofre elementar para obtenção de grupos tióis (-SH) na superficie dos referidos nanotubos (SWCNT-SH, DWCNT-SH, MWCNT-SH). Os nanotubos funcionalizados (NTCs-FUNC) apresentam diversas aplicações que incluem, mas não se limitam a servir de aporte reacional para ligação dos mesmos com moléculas e macromoléculas, de origem natural ou sintética, tais como: carboidratos, polímeros, aminoácidos, peptideos, proteínas, enzimas o anticorpos; para a formação de sistemas híbridos multifuncionais, aplicados ao transporte de fármacos e agroquímicos, por exemplo.WO2014117234 (A1)B82Y30/00B82Y40/00WO2013BR00535B82Y30/00B82Y40/00WO2008048227 (A2

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound-An In Vitro Study

: In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 50 -Se- (phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA77KL-NPs presented nanometric size (around 120 nm), polydispersity index values < 0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACATSe-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin