PUBLICATION
Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo
- Authors
- Lee, J.Y., Ham, J., Lim, W., Song, G.
- ID
- ZDB-PUB-200522-9
- Date
- 2020
- Source
- Free radical biology & medicine 154: 95-104 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Apomorphine, Epithelial ovarian cancer, Mitochondrial dysfunction
- MeSH Terms
-
- Animals
- Apomorphine*/pharmacology
- Apoptosis
- Carcinoma, Ovarian Epithelial/drug therapy
- Cell Line, Tumor
- Cell Proliferation
- Electron Transport
- Female
- Humans
- Ovarian Neoplasms*/drug therapy
- Zebrafish
- PubMed
- 32437927 Full text @ Free Radic. Biol. Med.
Citation
Lee, J.Y., Ham, J., Lim, W., Song, G. (2020) Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo. Free radical biology & medicine. 154:95-104.
Abstract
Apomorphine, a therapeutic agent for neurological diseases, is structurally similar to dopamine, and thereby holds potential in cancer therapy. However, there are no reports regarding its anti-cancer effects on human epithelial ovarian cancers (EOCs); therefore, we aimed to elucidate the mechanism underlying its action after drug repositioning. Apomorphine inhibited the proliferation of ES2 and OV90 EOC cells by inducing caspase activation and mitochondrion-associated apoptosis; it also promoted endoplasmic reticulum stress and mitochondrial dysfunction through mitochondrial membrane potential depolarization and mitochondrial calcium overload. Moreover, following apomorphine treatment, we noted the loss of respiratory chain activity by reduction of oxidative phosphorylation and energy-production shift in EOC cells. Further, we verified the anti-angiogenic capacity of apomorphine using fli:eGFP transgenic zebrafish. As a preclinical assessment, we demonstrated the synergistic anti-cancer effects of apomorphine and paclitaxel combination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping