The Microbiota-Derived Metabolite of Quercetin, 3,4-Dihydroxyphenylacetic Acid Prevents Malignant Transformation and Mitochondrial Dysfunction Induced by Hemin in Colon Cancer and Normal Colon Epithelia Cell Lines
Author
dc.contributor.author
Catalán Díaz, Mabel
Author
dc.contributor.author
Ferreira, Jorge
Author
dc.contributor.author
Carrasco Pozo, Catalina
Admission date
dc.date.accessioned
2021-03-24T21:32:47Z
Available date
dc.date.available
2021-03-24T21:32:47Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Molecules 2020, 25, 4138
es_ES
Identifier
dc.identifier.other
10.3390/molecules25184138
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/178775
Abstract
dc.description.abstract
Meat diet plays a pivotal role in colorectal cancer (CRC). Hemin, a metabolite of myoglobin, produced after meat intake, has been involved in CRC initiation. The compound, 3,4-dihydroxyphenylacetic acid (3,4HPAA) is a scarcely studied microbiota-derived metabolite of the flavonoid quercetin (QUE), which exert antioxidant properties. The aim of this study was to determine the protective effect of 3,4HPAA against malignant transformation (increased cell proliferation, decreased apoptosis, DNA oxidative damage and augmented reactive oxidative species (ROS) levels) and mitochondrial dysfunction induced by hemin in normal colon epithelial cells and colon cancer cells. The effect of 3,4HPAA was assessed in comparison to its precursor, QUE and to a known CRC protective agent, sulforaphane (SFN). The results showed that both, tumor and normal cells, exposed to hemin, presented increased cell proliferation, decreased caspase 3 activity and cytochrome c release, as well as augmented production of intracellular and mitochondrial ROS. In addition, hemin decreased the mitochondrial membrane potential (MMP) and the activity of complexes I and II of the electron transport chain. These effects of hemin were prevented by the action of 3,4HPAA. The metabolite showed to be more active than QUE and slightly less active than SFN. In conclusion, 3,4HPAA administration could represent a promising strategy for preventing malignant transformation and mitochondrial dysfunction in colon epithelia induced by hemin.
es_ES
Patrocinador
dc.description.sponsorship
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
11160281
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
1180296
Malignant transformation and mitochondrial dysfunction
es_ES
Título
dc.title
The Microbiota-Derived Metabolite of Quercetin, 3,4-Dihydroxyphenylacetic Acid Prevents Malignant Transformation and Mitochondrial Dysfunction Induced by Hemin in Colon Cancer and Normal Colon Epithelia Cell Lines