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Author: search.filters.author.Flavio CarriónSubject: search.filters.subject.cytotoxicity

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    Surface Immunogenic Protein of Streptococcus Group B is an Agonist of Toll-Like Receptors 2 and 4 and a Potential Immune Adjuvant
    (2020)
    Diego A. Diaz-Dinamarca
    ;
    Ricardo A. Manzo
    ;
    Daniel A. Soto
    ;
    María José Avendaño-Valenzuela
    ;
    Diego N. Bastias
    <jats:p>Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B Streptococcus (GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines.</jats:p>
      7Scopus© Citations 8
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    Epanorin, a lichen secondary metabolite, inhibits proliferation of MCF-7 breast cancer cells.
    (2019)
    Juan Palacios-Moreno
    ;
    Cecilia Rubio
    ;
    Wanda Quilhot
    ;
    M. Fernanda Cavieres
    ;
    Eduardo de la Peña
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Epanorin (EP) is a secondary metabolite of the <jats:italic>Acarospora</jats:italic> lichenic species. EP has been found in lichenic extracts with antimicrobial activity, and UV-absorption properties have been described for closely related molecules; however, its antiproliferative activity in cancer cells has not yet been explored. It has been hypothesized that EP inhibits cancer cell growth. MCF-7 breast cancer cells, normal fibroblasts, and the non-transformed HEK-293 cell line were exposed to increasing concentrations of EP, and proliferation was assessed by the sulforhodamine-B assay.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>MCF-7 cells exposed to EP were examined for cell cycle progression using flow cytometry, and DNA fragmentation was examined using the TUNEL assay. In addition, EP’s mutagenic activity was assessed using the <jats:italic>Salmonella typhimurium</jats:italic> reverse mutation assay. The data showed that EP inhibits proliferation of MCF-7 cells, and it induces cell cycle arrest in G0/G1 through a DNA fragmentation-independent mechanism. Furthermore, EP’s lack of overt cytotoxicity in the normal cell line HEK-293 and human fibroblasts in cell culture is supported by the absence of mutagenic activity of EP.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>EP emerges as a suitable molecule for further studies as a potential antineoplastic agent.</jats:p> </jats:sec>
    Scopus© Citations 7  20