Browsing by Author "Guzman, Leda"

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    In vitro evaluation and molecular docking of QS-21 and quillaic acid from Quillaja saponaria Molina as gastric cancer agents
    (NATURE RESEARCH, 2020) Guzman, Leda; Villalon, Katherine; Jose Marchant, Maria; Elena Tarnok, Maria; Cardenas, Pilar; Aquea, Gisela; Acevedo, Waldo; Padilla, Leandro; Bernal, Giuliano; Molinari, Aurora; Corvalan, Alejandro
    The cytotoxic mechanism of the saponin QS-21 and its aglycone quillaic acid (QA) was studied on human gastric cancer cells (SNU1 and KATO III). Both compounds showed in vitro cytotoxic activity with IC50 values: 7.1 mu M (QS-21) and 13.6 mu M (QA) on SNU1 cells; 7.4 mu M (QS-21) and 67 mu M (QA) on KATO III cells. QS-21 and QA induce apoptosis on SNU1 and KATO III, as demonstrated by TUNEL, Annexin-V and Caspase Assays. Additionally, we performed in silico docking studies simulating the binding of both triterpenic compounds to key proteins involved in apoptotic pathways. The binding energies (G(bin)) thus calculated, suggest that the pro-apoptotic protein Bid might be a plausible target involved in the apoptotic effect of both triterpenic compounds. Although QA shows some antiproliferative effects on SNU1 cells cultured in vitro, our results suggest that QS-21 is a more powerful antitumor agent, which merits further investigation regarding their properties as potential therapeutic agents for gastric cancer.
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    Involvement of several transcriptional regulators in the differential expression of tfd genes in Cupriavidus necator JMP134
    (2009) Trefault, Nicole; Guzman, Leda; Perez, Heidi; Godoy, Margarita; Gonzalez, Bernardo
    Cupriavidus necator JMP134 has been extensively studied because of its ability to degrade chloroaromatic compounds, including the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 3-chlorobenzoic acid (3-CB), which is achieved through the pJP4-encoded chlorocatechol degradation gene clusters: tfdC(I)D(I)E(I)F(I), and tfdD(II)C(II)E(II)F(II). The present work describes a different tfd-genes expression profile depending on whether C. necator cells were induced with 2,4-D or 3-CB. By contrast, in vitro binding assays of the Purified transcriptional activator TfdR showed similar binding to both tfd intergenic regions; these results were confirmed by in Vivo Studies of the expression of transcriptional lacZ fusions for these intergenic regions. Experiments aimed at investigating whether other pJP4 plasmid or chromosomal regulatory proteins could contribute to the differences in the response of both tfd promoters to induction by 2,4-D and 3-CB showed that the transcriptional regulators from the benzoate degradation pathway, CatR I and CatR2, affected 3-CB- and 2,4-D-related growth capabilities. It was also determined that the ISJP4-interrupted protein TfdT decreased growth on 3-CB. In addition, an ORF with 34% amino acid identity to IcIR-type transcriptional regulator members and located near the tfd(II) gene cluster module was shown to modulate the 2,4-D growth capability. Taken together, these results Suggest that tfd transcriptional regulation in C. necator JMP134 is far more complex than previously thought and that it involves proteins from different transcriptional regulator families. [Int Microbiol 2009; 12(2):97-106]