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.
Translated title of the contributionFactor inducible por hipoxia HIF-1α modula la resistencia a los medicamentos en las células de cáncer de colon.
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

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