PUBLICATION
Targeting the Redox Balance Pathway Using Ascorbic Acid in sdhb Zebrafish Mutant Larvae
- Authors
- Dona, M., Lamers, M., Rohde, S., Gorissen, M., Timmers, H.J.L.M.
- ID
- ZDB-PUB-211025-32
- Date
- 2021
- Source
- Cancers 13(20): (Journal)
- Registered Authors
- Dona, Margo, Gorissen, Marnix, Timmers, Henri
- Keywords
- Vitamin C, cancer, drug discovery, mitochondrial complex II, paraganglioma, phaeochromocytoma, redox balance pathway, therapy, zebrafish
- MeSH Terms
- none
- PubMed
- 34680273 Full text @ Cancers
Citation
Dona, M., Lamers, M., Rohde, S., Gorissen, M., Timmers, H.J.L.M. (2021) Targeting the Redox Balance Pathway Using Ascorbic Acid in sdhb Zebrafish Mutant Larvae. Cancers. 13(20):.
Abstract
Patients with mutations in the β-subunit of the succinate dehydrogenase (SDHB) have the highest risk to develop incurable malignant phaeochromocytomas and paragangliomas (PPGLs). Therapy development is hindered by limited possibilities to test new therapeutic strategies in vivo. One possible molecular mechanism of SDHB-associated tumorigenesis originates in an overproduction of reactive oxygen species (ROS) due to mitochondrial dysfunction. Ascorbic acid (Vitamin C) has already been shown to act as anti-cancer agent in several clinical trials for various types of cancer. In this study, the potential of the sdhbrmc200 zebrafish model to study SDHB-associated PPGLs using a drug screening approach was investigated. First, we identified increased basal ROS levels in homozygous sdhb larvae compared to heterozygous and wild-type siblings. Using a semi high-throughput drug screening, the effectiveness of different dosages of anti- and pro-oxidant Vitamin C were assessed to evaluate differences in survival, ROS levels, and locomotor activity. Low-dosage levels of Vitamin C induced a decrease of ROS levels but no significant effects on lifespan. In contrast, high-dosage levels of Vitamin C shortened the lifespan of the homozygous sdhbrmc200 larvae while not affecting the lifespan of heterozygous and wild-type siblings. These results validated the sdhbrmc200 zebrafish model as a powerful drug screening tool that may be used to identify novel therapeutic targets for SDHB-associated PPGLs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping