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Nordihydroguaiaretic Acid Affects Undifferentiated and Differentiated Neuroblastoma Cells Differently through Mechanisms that Impact on Cell Viability.
Ferrera, Patricia; De la Fuente-Muñoz, César Espino; Arias, Clorinda.
Afiliación
  • Ferrera P; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, CDMX, Mexico.
  • De la Fuente-Muñoz CE; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, CDMX, Mexico.
  • Arias C; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, CDMX, Mexico.
CNS Neurol Disord Drug Targets ; 23(9): 1167-1175, 2024.
Article en En | MEDLINE | ID: mdl-38151851
ABSTRACT

AIM:

We aimed to investigate the mechanisms involved in the neurotoxic effects of NDGA on differentiated and undifferentiated human neuroblastoma cells (MSN), assessing cell viability, changes in the actin cytoskeleton, cell migration and the expression of the 5-LOX enzyme and the inhibitor of cell cycle progression p21WAF1/CIP1.

BACKGROUND:

High expression and activity of the lipoxygenase enzyme (LOX) have been detected in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has been extensively tested as an antiproliferative drug against diverse types of cancer cells.

OBJECTIVE:

In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that did not affect cell survival when they differentiated to a neuron-like phenotype and the potential mechanisms involved in the anticancer properties.

METHODS:

We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor p21WAF1/CIP1 and 5-LOX.

RESULTS:

We found that differentiated human neuroblastoma cells are more resistant to NDGA than undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration, changes in actin cytoskeleton morphology, induction of p21WAF1/CIP1 and decreased levels of the 5-LOX enzyme.

CONCLUSION:

This study provides new evidence regarding the potential use of NDGA to induce cell death in human neuroblastoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Masoprocol / Diferenciación Celular / Movimiento Celular / Supervivencia Celular / Neuroblastoma Límite: Humans Idioma: En Revista: CNS Neurol Disord Drug Targets Asunto de la revista: NEUROLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Emiratos Árabes Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Masoprocol / Diferenciación Celular / Movimiento Celular / Supervivencia Celular / Neuroblastoma Límite: Humans Idioma: En Revista: CNS Neurol Disord Drug Targets Asunto de la revista: NEUROLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Emiratos Árabes Unidos