<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0123-3475</journal-id>
<journal-title><![CDATA[Revista Colombiana de Biotecnología]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. colomb. biotecnol]]></abbrev-journal-title>
<issn>0123-3475</issn>
<publisher>
<publisher-name><![CDATA[Instituto de Biotecnología, Universidad Nacional de Colombia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0123-34752020000200006</article-id>
<article-id pub-id-type="doi">10.15446/rev.colomb.biote.v22n2.73114</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Señuelo dirigido a HIF-1 potencializa efectos citotóxicos de dos agentes quimioterapéuticos en MDA-MB-231]]></article-title>
<article-title xml:lang="en"><![CDATA[HIF decoy improve cytotoxic effects of two chemotherapeutic agents on MDA-MB-231]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González]]></surname>
<given-names><![CDATA[Diana Mayorga]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Parra]]></surname>
<given-names><![CDATA[Michael Ramírez]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gutiérrez]]></surname>
<given-names><![CDATA[Fabio A. Aristizábal]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad Nacional de Colombia Facultad de Ciencias Departamento de Farmacia]]></institution>
<addr-line><![CDATA[Bogotá ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad Nacional de Colombia Facultad de Ciencias Departamento de Farmacia]]></institution>
<addr-line><![CDATA[Bogotá ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad Nacional de Colombia Facultad de Ciencias Departamento de Farmacia]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<volume>22</volume>
<numero>2</numero>
<fpage>6</fpage>
<lpage>17</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0123-34752020000200006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0123-34752020000200006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0123-34752020000200006&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN Procesos oncogénicos como proliferación incontrolable, resistencia apoptótica, aumento de mecanismos angiogénicos y evasión inmune son regulados generalmente por factores de transcripción, como HIF-1. Por tanto, se ha señalado a esta molécula como un blanco terapéutico prometedor. Para explorar esta posibilidad, un oligonucleótido tipo "señuelo" dirigido a HIF-1 a (ODN) fue diseñado para evaluar su eficiencia en esquema tanto monoterapéutico, como en combinación con dos agentes quimioterapéuticos en un modelo in vitro de cáncer de mama. Después de comprobar, mediante citometría de flujo e inmunofluorescencia, la localización del blanco, el señuelo fue transfectado en la línea celular MDA-MB-231. Se estableció la IC-50 de HIF-1 a ODN, Cisplatino y Taxol con el método de Resazurina. Mecanismos de muerte celular fueron evaluados con el método de TUNEL. Por último, se estableció el índice de combinación (IC) de cada uno de los quimio-agentes en combinación con el ODN. Se evidencio que HIF-1 a ODN causa un efecto citotóxico en MDA-MB-231 de hasta un 90% hacia las 72h pos-tratamiento. Este efecto no se observa tanto en los controles del ensayo, como en el cultivo primario de células no tumorales (FIBRO), siendo este agente altamente selectivo hacia células tumorales, al activar mecanismos pro-apoptóticos. A su vez, HIF-1 a ODN potencializa la actividad tumorogénica de Cisplatino y Taxol en la línea celular tumoral. Por tanto, HIF-1 a ODN demostró tener actividad selectiva potencialmente antitumoral, al disminuir la proliferación celular e inducir apoptosis; optimizando de forma sinérgica, la eficacia de fármacos quimioterapéuticos de alto espectro, en tratamientos combinados.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT Oncogenic processes like uncontrollable proliferation, resistance to apoptosis, increases in angiogenic mechanisms and immune evasion are regulated by transcription factors such HIF-1. Therefore, this molecule is regarded as a potential therapeutic target. To explore this possibility, a HIF-1 &#945; oligonucleotide decoy (ODN) was designed to evaluate its efficiency on both a mono-therapeutic scheme and a mixed treatment with two chemotherapeutic agents within an in vitro model of breast cancer. After confirming the target location with flow cytometry and immunofluorescence assays, that decoy was transfected over the MDA-MB-231 cell line. We established the HIF-1 &#945; ODN, Cisplatin and Taxol IC-50 using Resazurin tests. Cell death mechanisms was evaluated with TUNEL. Finally, we obtained the combination index (IC) of each chemical agents with the ODN. This study showed that HIF-1 &#945; ODN caused a cytotoxic effect (up to 90%) in MDA-MB-231 during 72 hours post treatment. That effect did not appear in either the assay controls nor in non-tumor cell cultures (FIBRO). This agent is highly selective towards tumor cells, activating pro-apoptotic mechanisms. Additionally, HIF-1 &#945; ODN increases the tumorigenic action of Cisplatin and Taxol on the cell line, due to an additive effect. For these reasons, HIF-1 &#945; ODN has potential antitumor selective activity, decreasing cell proliferation, inducing apoptosis, and optimizing, in a synergistic manner, the efficacy of wide spectrum chemotherapeutic compounds when it used in a combined treatment.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Cáncer]]></kwd>
<kwd lng="es"><![CDATA[hipoxia]]></kwd>
<kwd lng="es"><![CDATA[proliferación celular]]></kwd>
<kwd lng="es"><![CDATA[apoptosis]]></kwd>
<kwd lng="es"><![CDATA[sinergia]]></kwd>
<kwd lng="en"><![CDATA[Cancer]]></kwd>
<kwd lng="en"><![CDATA[hypoxia]]></kwd>
<kwd lng="en"><![CDATA[cell proliferation]]></kwd>
<kwd lng="en"><![CDATA[apoptosis]]></kwd>
<kwd lng="en"><![CDATA[synergy]]></kwd>
</kwd-group>
</article-meta>
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