PUBLICATION
Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling
- Authors
- Jiang, L.L., Li, K., Lin, Q.H., Ren, J., He, Z.H., Li, H., Shen, N., Wei, P., Feng, F., He, M.F.
- ID
- ZDB-PUB-160612-2
- Date
- 2016
- Source
- Reproductive toxicology (Elmsford, N.Y.) 63: 161-8 (Journal)
- Registered Authors
- Keywords
- Bioconcentration, Gambogic acid, RA signaling, Teratogenic toxicity, Zebrafish
- MeSH Terms
-
- Animal Fins/drug effects*
- Animal Fins/embryology
- Animals
- Antineoplastic Agents/toxicity*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects
- Gene Expression Regulation, Developmental/drug effects
- Retinal Dehydrogenase/genetics
- Retinoic Acid 4-Hydroxylase/genetics
- Signal Transduction/drug effects
- Tretinoin/metabolism*
- Xanthones/toxicity*
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 27288890 Full text @ Reprod. Toxicol.
Citation
Jiang, L.L., Li, K., Lin, Q.H., Ren, J., He, Z.H., Li, H., Shen, N., Wei, P., Feng, F., He, M.F. (2016) Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling. Reproductive toxicology (Elmsford, N.Y.). 63:161-8.
Abstract
Gambogic acid (GA), the major active ingredient of gamboge, has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients due to its strong anticancer activity. However, our previous research showed that GA was teratogenic against zebrafish fin development. To explore the teratogenicity and the underlying mechanisms, zebrafish (Danio rerio) embryos were used. The morphological observations revealed that GA caused fin defects in zebrafish embryos in a concentration-dependent manner. The critical exposure time of GA to reveal teratogenicity was before 8 hpf (hours post fertilization). LC/MS/MS analysis revealed that a maximum bioconcentration of GA was occurred at 4 hpf. Q-PCR data showed that GA treatment resulted in significant inactivation of RA signaling which could be partially rescued by the exogenous supply of RA. These results indicate the potential teratogenicity of GA and provide evidence for a caution in its future clinic use.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping