Browsing by Author "Martin, Jesus"
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- High-content screening of natural products reveals novel nuclear export inhibitorsPublication . Cautain, Bastien; de Pedro, Nuria; Garzon, Virginia Murillo; de Escalona, Maria Munoz; Menendez, Victor Gonzalez; Tormo, Jose R.; Martin, Jesus; El Aouad, Noureddine; Reyes, Fernando; Asensio, Francisco; Genilloud, Olga; Vicente, Francisca; Link, WolfgangNatural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-B, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 mu M. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.
- Physicochemical characteristics and antiproliferative and antioxidant activities of Moroccan Zantaz honey rich in methyl syringatePublication . Elamine, Youssef; Lyoussi, Badiaa; Miguel, Maria G.; Anjos, Ofelia; Estevinho, Leticia; Alaiz, Manuel; Giron-Calle, Julio; Martin, Jesus; Vioque, JavierZantaz honey is a monofloral variety produced from the melliferous plant Bupleurum spinosum (Apiaceae), a shrub that grows mainly in the Atlas Moroccan Mountains. Determination of the polyphenol composition revealed that methyl syringate accounts for more than 50% of total polyphenols, which represents a very useful parameter for the characterization of this monofloral honey. Epicatechin, syringic acid and catechin are also abundant. Caco-2 and THP-1 cells were used for determination of antioxidant and antiproliferative activities in Zantaz honey, respectively. All six commercial samples that were used for these studies exhibited antioxidant activity and inhibited cell proliferation. Interestingly, these activities had a positive correlation mainly with the content in methyl syringate and gallic acid. The recognition of health promoting activities in Zantaz honey should increase its commercial value, which would have a positive economic impact on the poor rural communities of Morocco where it is produced.