Antimetastatic effects of cordycepin mediated by the inhibition of mitochondrial activity and estrogen-related receptor α in human ovarian carcinoma cells

Abstract

// Chia-Woei Wang 1, 2 , Wei-Hsuan Hsu 3 , Chen-Jei Tai 1, 2, 4, 5 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan 2 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan 3 Biochemical Process Technology Department, Center of Excellence for Drug Development, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 30068, Taiwan 4 Department of Traditional Chinese Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11042, Taiwan 5 Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11042, Taiwan Correspondence to: Chen-Jei Tai, email: chenjtai@tmu.edu.tw Keywords: cordycepin, mitochondrial fusion, mitochondrial fission, estrogen-related receptor (ERR)-α, antimigration Received: September 16, 2016      Accepted: November 23, 2016      Published: December 09, 2016 ABSTRACT Cordycepin (3′-deoxyadenosine) is a compound for antitumor, which has been found to exert antiangiogenic, antimetastatic, and antiproliferative effects, as well as inducing apoptosis. However, the association between cancer metastasis and mitochondrial activity in cordycepin-treated ovarian carcinoma cells remains unclear. The 50 and 100 μM of cordycepin inhibits mitochondrial fusion and induces mitochondrial fission, respectively. These suggested that cordycepin showed the down-regulation of mitochondrial function and limitation of energy production. Because of activation of mitochondria and generation of energy are needed in cancer cell migration/invasion. After 24 h treatment, cordycepin suppresses epithelial–mesenchymal transition and migration in ovarian carcinoma cells through inhibiting estrogen-related receptor (ERR)-α. The ERRα is a co-transcription factor for gene expressions associated with mitochondrial fusion. Our results indicate that cordycepin suppresses metastasis and migration of ovarian carcinoma cells via inhibiting mitochondrial activity in non-toxic concentrations, and cordycepin has potential benefits in ovarian cancer therapy.