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

Martha Leonor Pinzón-Daza, Yenith Cuellar, Alejandro Ondo, Luisa Matheus, Lilia Del Riesgo, Fabio Castillo, Ruth Garzón

Producción científica: Contribución a una revistaArtículo de Investigaciónrevisión exhaustiva

2 Citas (Scopus)

Resumen

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 Cobalt(II) chloride (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.
Idioma originalInglés estadounidense
Páginas (desde-hasta)543-550
Número de páginas8
PublicaciónRevista Facultad de Medicina
Volumen66
N.º4
DOI
EstadoPublicada - oct. 1 2018

Áreas temáticas de ASJC Scopus

  • Medicina General

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