Gambogic acid causes fin developmental defect in zebrafish embryo partially via retinoic acid signaling.
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.
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.
Ling-Ling
LL
Jiang
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.
Kang
K
Li
Department of Phytochemistry, China Pharmaceutical University, Nanjing 210009, PR China.
Qing-Hua
QH
Lin
Jiangsu Simovay Co. Ltd, Nanjing 210042, PR China.
Jian
J
Ren
School of Medicine, Yale University, New Haven, CT 06511,USA.
Zhi-Heng
ZH
He
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.
Huan
H
Li
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.
Ning
N
Shen
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.
Ping
P
Wei
Department of Phytochemistry, China Pharmaceutical University, Nanjing 210009, PR China.
Feng
F
Feng
Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China. Electronic address: mingfanghe@njtech.edu.cn.
Ming-Fang
MF
He
D058500:Animal Fins / Q000187:drug effects* / Q000196:embryology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D050697:Retinal Dehydrogenase / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism*; D044004:Xanthones / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D000970:Antineoplastic Agents; D044004:Xanthones; D029961:Zebrafish Proteins; D014212:Tretinoin; C052659:gambogic acid; D000072516:Retinoic Acid 4-Hydroxylase; D050697:Retinal Dehydrogenase
Bioconcentration; Fin development; Gambogic acid; LC–MS/MS; RA signaling; Teratogenic toxicity; Zebrafish