Apomorphine facilitates loss of respiratory chain activity in human epithelial ovarian cancer and inhibits angiogenesis in vivo: Apomorphine suppresses ovarian cancer via multiple intracellular mechanisms

Jin Young Lee, Jiyeon Ham, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalFree Radical Biology and Medicine
Volume154
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • Angiogenesis
  • Apomorphine
  • Epithelial ovarian cancer
  • Mitochondrial dysfunction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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