Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology.
Local danazol therapy reduces the signs and symptoms of endometriosis without inhibition of regular ovulation and menstruation and without atrophic changes to the endometrium or vaginal wall. It has been suggested that danazol has possible non-cytotoxic direct actions on eutopic endometrial cells and endometriotic cells. We have investigated the direct effects of danazol on a human endometrial epithelial cell line, HHUA, which is believed to retain many normal intracellular signaling pathways. A thoroughly dissolved solution of danazol enhanced Fas-mediated apoptosis in HHUA cells without inhibiting cell proliferation. Semi-quantitative flow cytometric analysis revealed that danazol did not enhance cell surface expression of Fas antigens. The enhancement of Fas-mediated apoptosis by endometrial cytokines such as EGF, IL-1beta and interferon-gamma was not additively enhanced by danazol; nor did danazol enhance growth suppression by anticancer drugs such as paclitaxel, carboplatin and 5-fluorouracil. Moreover, danazol did not enhance the irradiation-induced cell growth suppression of radiation-sensitive human cervical squamous cancer ME180 cells. These results indicate that danazol may regulate endometrial epithelial cell proliferation and apoptosis within normal physiology.
Tanaka
Tetsuji
T
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan. obgywmu@wakayama-med.ac.jp
Umesaki
Naohiko
N
D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines; D003613:Danazol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
D016207:Cytokines; D019014:fas Receptor; D003613:Danazol