Hypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells

Martha Leonor Pinzon Daza, Yenith Cuellar-Saenz, Alejandro Ondo-Méndez, Luisa Marina Matheus Merino, Lilia Del Riesgo Prendes, Fabio Castillo Rivera, Ruth Elizabeth Garzon Fernandez

Research output: Contribution to journalArticle

Abstract

Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.

Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.

Materials and methods: HT29 colon cancer cells were treated with CoCl2 or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.

Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.

Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.
Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalRevista de la Facultad de Medicina
Volume66
Issue number4
Early online dateDec 19 2018
DOIs
StatePublished - 2018

Cite this

Pinzon Daza, Martha Leonor ; Cuellar-Saenz, Yenith ; Ondo-Méndez, Alejandro ; Matheus Merino, Luisa Marina ; Del Riesgo Prendes, Lilia ; Castillo Rivera, Fabio ; Garzon Fernandez, Ruth Elizabeth. / Hypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells. In: Revista de la Facultad de Medicina. 2018 ; Vol. 66, No. 4. pp. 543-550.
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abstract = "Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.Materials and methods: HT29 colon cancer cells were treated with CoCl2 or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.",
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Hypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells. / Pinzon Daza, Martha Leonor; Cuellar-Saenz, Yenith; Ondo-Méndez, Alejandro; Matheus Merino, Luisa Marina; Del Riesgo Prendes, Lilia; Castillo Rivera, Fabio; Garzon Fernandez, Ruth Elizabeth.

In: Revista de la Facultad de Medicina, Vol. 66, No. 4, 2018, p. 543-550.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hypoxia-inducible factor HIF-1α modulates drugs resistance in colon cancer cells

AU - Pinzon Daza, Martha Leonor

AU - Cuellar-Saenz, Yenith

AU - Ondo-Méndez, Alejandro

AU - Matheus Merino, Luisa Marina

AU - Del Riesgo Prendes, Lilia

AU - Castillo Rivera, Fabio

AU - Garzon Fernandez, Ruth Elizabeth

PY - 2018

Y1 - 2018

N2 - Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.Materials and methods: HT29 colon cancer cells were treated with CoCl2 or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.

AB - Introduction: Drug resistance mechanisms may be associated with decreased cell death and its induction may depend on the response to oxidative stress caused by hypoxia. The correlation between hypoxia-inducible factor HIF-1α, the number of reactive oxygen species and their effect on cell survival has not yet been evaluated.Objective: The purpose of this study was to evaluate the effect of HIF-1α activity and reactive oxygen species (ROS) accumulation in apoptosis of colon cancer cells.Materials and methods: HT29 colon cancer cells were treated with CoCl2 or doxorubicin and the activity of HIF-1α was determined by ELISA assay. ROS were determined using fluorescence probe carboxy-H2DFFDA. Apoptosis was assessed by caspase-3 activation analysis, and PUMA and BAX mRNA levels by qRT-PCR. The reduction of the antiapoptotic effect due to hypoxia was attenuated by use of the endonuclease APE-1 (E3330) inhibitor. The endonuclease E3330 APE-1 inhibitor allowed evaluating the effect of ROS generated by doxorubicin and CoCl2 on apoptosis.Results: Chemical hypoxia in combination with doxorubicin is an oxidative stressor in HT29 cells and induces a reduction in the apoptotic process in a time-dependent manner.Conclusion: Resistance to hypoxia and doxorubicin-mediated cell death could be controlled by a mechanism related to the activity of HIF-1α and the amount of reactive oxygen species generated.

U2 - https://doi.org/10.15446/revfacmed.v66n4.55149

DO - https://doi.org/10.15446/revfacmed.v66n4.55149

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SP - 543

EP - 550

JO - Revista de la Facultad de Medicina

JF - Revista de la Facultad de Medicina

SN - 0120-0011

IS - 4

ER -