Acellular fraction of ovarian cancer ascites induce apoptosis by activating JNK and inducing BRCA1, Fas and FasL expression in ovarian cancer cells
Marie Cohen1, Sandra Pierredon1, Christine Wuillemin1, Florence Delie2, Patrick Petignat1
1 Department of Gynecology-Obstetrics, faculty of medicine, Geneva, Switzerland
2 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva,Switzerland.
Keywords: apoptosis, ascites, JNK, Fas, FasL, BRCA1
Received: March 18, 2014 Accepted: April 28, 2014 Published: April 30, 2014
Acellular fraction of ascites might play an active role in tumor development. Nevertheless the mechanisms involved in the tumor-modulating properties are still controversial. Here, we demonstrate that malignant ascites from 8 patients with epithelial ovarian cancer did not influence proliferative or invasive properties of ovarian cancer cells, but promoted H2O2-induced apoptosis and increased sensitivity to paclitaxel. Malignant ascites induced BRCA1, Fas and FasL expression and phosphorylation of JNK, but not the activation of caspase pathway. Ascites-induced apoptosis of ovarian cancer cells was strongly inhibited by a JNK inhibitor suggesting a critical role of JNK pathway in ascite-induced apoptosis. The use of siRNA JNK confirmed the importance of JNK in ascites-induced Fas and FasL expression. These results demonstrate that malignant ascites induce apoptosis of ovarian cancer cells and encourage us to think about the clinical management of ovarian cancer patients with malignant ascites.