Apomorphine induces mitochondrial-dysfunction-dependent apoptosis in choriocarcinoma

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  • 1 Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  • 2 Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
  • 3 Department of Food and Nutrition, Kookmin University, Seoul, Republic of Korea

Correspondence should be addressed to W Lim: ghsong@korea.ac.kr or to G Song: ghsong@korea.ac.kr

*(J-Y Lee and J Ham contributed equally to this work)

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Apomorphine is a derivative of morphine that is used for the treatment of Parkinson’s disease because of its effects on the hypothalamus. Therapeutic effects of apomorphine have also been reported for various neurological diseases and cancers. However, the molecular mechanisms of the antitumor effects of apomorphine are not clear, especially with respect to choriocarcinoma. This is the first study to elucidate the anticancer effects of apomorphine on choriocarcinoma. We found that apomorphine suppressed the viability, proliferation, ATP production, and spheroid formation of JEG3 and JAR choriocarcinoma cells. Moreover, apomorphine activated the intrinsic apoptosis pathway by activating caspases and inhibited the production of anti-apoptotic proteins in choriocarcinoma cells. Further, apomorphine caused depolarization of mitochondria, calcium overload, energy deprivation, and endoplasmic reticulum stress in JEG3 and JAR cells. We confirmed synergistic effects of apomorphine with paclitaxel, a traditional chemotherapeutic agent, and propose that apomorphine could be a potential therapeutic agent in choriocarcinoma and an important candidate for drug repositioning that could help overcome resistance to conventional chemotherapy.

 

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