Nordihydroguaiaretic Acid Affects Undifferentiated and Differentiated Neuroblastoma Cells Differently through Mechanisms that Impact on Cell Viability

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - year:2023

Enthalten in:

CNS & neurological disorders drug targets - (2023) vom: 26. Dez.

Sprache:

Englisch

Beteiligte Personen:

Ferrera, Patricia [VerfasserIn]
De la Fuente-Muñoz, César Espino [VerfasserIn]
Arias, Clorinda [VerfasserIn]

Links:

Volltext

Themen:

5-LOX
Actin cytoskeleton
Human neuroblastoma cells
Journal Article
NDGA
P21

Anmerkungen:

Date Revised 28.12.2023

published: Print-Electronic

Citation Status Publisher

doi:

10.2174/0118715273268471231013135114

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366424998