Apomorphine induces mitochondrial-dysfunction-dependent apoptosis in choriocarcinoma
Jin-Young Lee1, Jiyeon Ham2, Whasun Lim3
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Reproduction (Cambridge, England)
|June 11, 2020
Summary
Apomorphine effectively combats choriocarcinoma by inducing cancer cell death and inhibiting growth. This study highlights its potential as a novel therapeutic agent, possibly overcoming chemotherapy resistance.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Apomorphine, a morphine derivative, is used for Parkinson's disease.
- Its anticancer effects are known but not fully understood, particularly in choriocarcinoma.
- This study investigates apomorphine's molecular mechanisms against choriocarcinoma.
Purpose of the Study:
- To elucidate the anticancer effects of apomorphine on choriocarcinoma cells.
- To investigate the molecular mechanisms underlying apomorphine's antitumor activity.
- To explore apomorphine's potential synergistic effects with conventional chemotherapy.
Main Methods:
- Assessing the impact of apomorphine on choriocarcinoma cell viability, proliferation, ATP production, and spheroid formation.
- Analyzing the activation of apoptosis pathways, including caspases and anti-apoptotic proteins.
- Investigating cellular stress responses such as mitochondrial depolarization, calcium overload, and endoplasmic reticulum stress.
Main Results:
- Apomorphine significantly suppressed choriocarcinoma cell viability, proliferation, ATP production, and spheroid formation.
- Apomorphine induced intrinsic apoptosis by activating caspases and reducing anti-apoptotic proteins.
- Apomorphine triggered mitochondrial dysfunction, calcium overload, energy depletion, and ER stress in choriocarcinoma cells.
Conclusions:
- Apomorphine exhibits potent anticancer effects against choriocarcinoma through multiple molecular pathways.
- Apomorphine demonstrates synergistic effects when combined with paclitaxel.
- Apomorphine is a promising candidate for drug repositioning in choriocarcinoma treatment, potentially overcoming chemoresistance.
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