{"corpus_id":121120559,"paper_sha":"05729d4ba352a2247d240c693dabbd5b4f273c21","doi":"10.1038/s41419-019-1526-0","arxiv_id":null,"pmid":31000722,"pmcid":"6472389","mag_id":2936505652,"dblp_id":null,"acl_id":null,"title":"Bromocriptine and cabergoline induce cell death in prolactinoma cells via the ERK/EGR1 and AKT/mTOR pathway respectively","year":2019,"publication_date":"2019-04-18","venue":"Cell Death and Disease","journal":{"name":"Cell Death & Disease","pages":null,"volume":"10"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":39,"citation_count":30,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Amino Acid Chloromethyl Ketones","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D000590"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Apoptosis","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D017209"},{"d":"Bromocriptine","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"},{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D001971"},{"d":"Cabergoline","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"},{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D000077465"},{"d":"Cell Line, Tumor","mj":false,"ui":"D045744"},{"d":"Early Growth Response Protein 1","mj":false,"qs":[{"q":"antagonists & inhibitors","mj":false,"ui":"Q000037"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051766"},{"d":"Extracellular Signal-Regulated MAP Kinases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D048049"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Nude","mj":false,"ui":"D008819"},{"d":"Microtubule-Associated Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008869"},{"d":"Pituitary Neoplasms","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D010911"},{"d":"Prolactinoma","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D015175"},{"d":"Proto-Oncogene Proteins c-akt","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051057"},{"d":"RNA Interference","mj":false,"ui":"D034622"},{"d":"RNA, Small Interfering","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D034741"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D015398"},{"d":"TOR Serine-Threonine Kinases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D058570"}],"chemicals":[{"n":"Amino Acid Chloromethyl Ketones","ui":"D000590","reg":"0"},{"n":"Early Growth Response Protein 1","ui":"D051766","reg":"0"},{"n":"Egr1 protein, rat","ui":"C486110","reg":"0"},{"n":"Microtubule-Associated Proteins","ui":"D008869","reg":"0"},{"n":"RNA, Small Interfering","ui":"D034741","reg":"0"},{"n":"benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone","ui":"C096713","reg":"0"},{"n":"Bromocriptine","ui":"D001971","reg":"3A64E3G5ZO"},{"n":"mTOR protein, rat","ui":"C546845","reg":"EC 2.7.1.1"},{"n":"Proto-Oncogene Proteins c-akt","ui":"D051057","reg":"EC 2.7.11.1"},{"n":"TOR Serine-Threonine Kinases","ui":"D058570","reg":"EC 2.7.11.1"},{"n":"Extracellular Signal-Regulated MAP Kinases","ui":"D048049","reg":"EC 2.7.11.24"},{"n":"Cabergoline","ui":"D000077465","reg":"LL60K9J05T"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/s41419-019-1526-0.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/05729d4ba352a2247d240c693dabbd5b4f273c21","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.","claims":[{"public_id":"cl_6aaaf7f32b374d157d56d61928ae068c","status":"active","text":"Bromocriptine induces apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas cabergoline induces autophagic death by inhibiting the AKT/mTOR signalling pathway.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_6aaaf7f32b374d157d56d61928ae068c"},{"public_id":"cl_eaae09df9a7533214b03d1103d7dbc76","status":"active","text":"Bromocriptine induces prolactinoma cell death mainly through the apoptosis pathway.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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