TY - JOUR
T1 - Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo
T2 - Apomorphine suppresses ovarian cancer via multiple intracellular mechanisms
AU - Lee, Jin Young
AU - Ham, Jiyeon
AU - Lim, Whasun
AU - Song, Gwonhwa
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Apomorphine
KW - Epithelial ovarian cancer
KW - Mitochondrial dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85085139036&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2020.05.001
DO - 10.1016/j.freeradbiomed.2020.05.001
M3 - Article
C2 - 32437927
AN - SCOPUS:85085139036
SN - 0891-5849
VL - 154
SP - 95
EP - 104
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -