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• W2153955918 abstract "Abstract Recently, we could show that gonadotropin-releasing hormone (GnRH)-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells in vitro and in vivo. In the present study, we have ascertained receptor binding and effects of GnRH-II antagonists on mitogenic signal transduction and on activation of proapoptotic protein Bax. The GnRH-II antagonists tested showed EC50 values for GnRH-I receptor binding in the range of 1 to 2 nmol/L. The GnRH-II agonist [d-Lys6]GnRH-II showed an EC50 value for GnRH-I receptor binding of ∼1,000 nmol/L. Agonistic activity on GnRH-I receptor function with an EC50 of 13 nmol/L has been determined for [d-Lys6]GnRH-II. Antagonistic activities with EC50 values in the range of 1 nmol/L were determined for the GnRH-II antagonists. Treatment of human endometrial, ovarian, and breast cancer cells with GnRH-II antagonists resulted in time-dependent activation of stress-induced mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase. In addition, treatment with GnRH-II antagonists induced time-dependent activation of proapoptotic protein Bax. GnRH-II antagonists are not involved in activation of protein kinase B/Akt or extracellular signal-regulated kinase 1/2. The GnRH-II antagonists tested had similar binding affinities to the GnRH-I receptor comparable with that of GnRH-I antagonist Cetrorelix. Referring to the cyclic AMP response element reporter gene activation assay, the GnRH-II agonist [d-Lys6]GnRH-II has to be classified as an agonist at the GnRH-I receptor, whereas the GnRH-II antagonists tested are clear antagonists at the GnRH-I receptor. GnRH-II antagonists induce apoptotic cell death in human endometrial, ovarian, and breast cancer cells via activation of stress-induced mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase followed by activation of proapoptotic protein Bax. [Cancer Res 2009;69(16):6473–81]" @default.
• W2153955918 created "2016-06-24" @default.
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• W2153955918 date "2009-08-12" @default.
• W2153955918 modified "2023-10-06" @default.
• W2153955918 title "GnRH-II Antagonists Induce Apoptosis in Human Endometrial, Ovarian, and Breast Cancer Cells via Activation of Stress-Induced MAPKs p38 and JNK and Proapoptotic Protein Bax" @default.
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• W2153955918 doi "https://doi.org/10.1158/0008-5472.can-08-4657" @default.
• W2153955918 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19638591" @default.
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