Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Luteinizing hormone-releasing hormone (LHRH) and its receptor are frequently expressed in human ovarian and endometrial cancers and are part of an autocrine mechanism of growth control. We have previously shown that the LHRH analog Triptorelin induces activation of nucleus factor kappa B (NFkappaB) and reduces apoptosis induced by doxorubicin in human ovarian cancer cells EFO-21 and EFO-27. The present study was performed to investigate the anti-apoptotic effects of LHRH analogs on apoptosis induced by doxorubicin, UV-light and ligation of CD95 in human endometrial and ovarian cancer cells. We further investigated the interaction of the LHRH system with the apoptotic pathway focusing on the effector-protease caspase 3. Doxorubicin (100 nM) induced apoptosis in the LHRH-receptor-positive human endometrial cancer cell line Ishikawa and in the human ovarian cancer cell lines EFO-21 and NIH:OVCAR-3. Pretreatment for 24 h with native LHRH, the LHRH agonist Triptorelin or the LHRH antagonist Cetrorelix (100 nM) significantly reduced apoptosis induced by doxorubicin in these cells. In EFO-21 cells pretreatment with 100 nM Triptorelin also reduced UV-light-induced apoptosis from 76% to 62.7% (p<0.01). EFO-21 cells express CD95. Cross-linking of CD95 with monoclonal antibody anti-APO-1 (500 ng/ml) increased apoptosis from spontaneous rate to 10.3% to 38.3% in EFO-21 cells (p<0.001). Pre-treatment with Triptorelin did not reduce CD95-mediated apoptosis in these cells. LHRH analogs protect human endometrial and ovarian cancer cells from DNA-replication-dependent cytotoxic agent and UV-light-induced apoptosis, but not from CD95-mediated apoptosis.
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PMID:Luteinizing hormone-releasing hormone (LHRH) inhibits apoptosis induced by cytotoxic agent and UV-light but not apoptosis mediated through CD95 in human ovarian and endometrial cancer cells. 1527 47