Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology

Masatake Tanaka, Tanaka T, Tetsuji Tanaka, Naohiko Umesaki, Umesaki N
International journal of molecular medicine · 1998 · vol. 23(2) , pp. 237–43 · doi:10.3892/ijmm_00000122 · PMID:19148548 · W2076840856
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Danazol enhanced Fas-mediated apoptosis in human endometrial epithelial cells without affecting cell proliferation or surface Fas expression.

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The paper investigated direct effects of danazol on a human endometrial epithelial cell line (HHUA) to test whether danazol can act non-cytotoxically on eutopic endometrial cells under normal signaling conditions. Using flow cytometry-based semi-quantitative analysis, the authors found that danazol enhanced Fas-mediated apoptosis in HHUA cells without inhibiting cell proliferation, and without increasing cell surface expression of Fas antigens. Danazol did not show additive effects on Fas-mediated apoptosis when combined with endometrial cytokines (EGF, IL-1β, interferon-γ), nor did it enhance growth suppression by anticancer drugs (paclitaxel, carboplatin, 5-fluorouracil) or irradiation-induced suppression in a radiation-sensitive cervical cancer line (ME180). This paper is centrally about endometriosis — it examines danazol’s proposed non-cytotoxic direct actions on endometrial epithelial cells in the context of danazol’s reported beneficial effects in endometriosis.

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Abstract

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.
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Print ISSN: 1107-3756 Online ISSN: 1791-244X International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease. International Journal of Oncology is an international journal devoted to oncology research and cancer treatment. Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery. Oncology Reports is an international journal devoted to fundamental and applied research in Oncology. Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine. Oncology Letters is an international journal devoted to Experimental and Clinical Oncology. Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology. International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis. Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology. Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition. Publishes open-access research on using epigenetics to advance understanding and treatment of human disease. An International Open Access Journal Devoted to General Medicine. Article - Authors: - Pages: 237-243|Published online on: February 1, 2009https://doi.org/10.3892/ijmm_00000122 - Expand metrics + 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-1β and interferon-γ 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. Copy and paste a formatted citation Spandidos Publications style Tanaka T and Umesaki N: Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology. Int J Mol Med 23: 237-243, 2009. APA Tanaka, T., & Umesaki, N. (2009). Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology. International Journal of Molecular Medicine, 23, 237-243. https://doi.org/10.3892/ijmm_00000122 MLA Tanaka, T., Umesaki, N."Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology". International Journal of Molecular Medicine 23.2 (2009): 237-243. Chicago Tanaka, T., Umesaki, N."Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology". International Journal of Molecular Medicine 23, no. 2 (2009): 237-243. https://doi.org/10.3892/ijmm_00000122

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Condition tags

endometriosis

MeSH descriptors

Apoptosis Danazol Endometrium Epithelial Cells fas Receptor Cell Line Cell Proliferation Cell Proliferation Cytokines Danazol Dose-Response Relationship, Drug Endometrium Endometrium Epithelial Cells Epithelial Cells fas Receptor Female Flow Cytometry Humans Signal Transduction

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