Repurposing of Bromocriptine for Cancer Therapy
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Ean-Jeong Seo
- Yoshikazu Sugimoto
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000446590700001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3389/fphar.2018.01030
- Externe Identifier
- Clarivate Analytics Document Solution ID: GW0WO
- PubMed Identifier: 30349477
- ISSN
- 1663-9812
- Zeitschrift
- FRONTIERS IN PHARMACOLOGY
- Schlüsselwörter
- drug repurposing
- ergot alkaloids
- bromocriptine
- neoplasms
- pharmacogenomics
- Artikelnummer
- ARTN 1030
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Repurposing of Bromocriptine for Cancer Therapy
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Ean-Jeong Seo
- Yoshikazu Sugimoto
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.3389/fphar.2018.01030
- eISSN
- 1663-9812
- Zeitschrift
- Frontiers in Pharmacology
- Online publication date
- 2018
- Status
- Published online
- Herausgeber
- Frontiers Media SA
- Herausgeber URL
- http://dx.doi.org/10.3389/fphar.2018.01030
- Datum der Datenerfassung
- 2022
- Titel
- Repurposing of Bromocriptine for Cancer Therapy
- Ausgabe der Zeitschrift
- 9
Datenquelle: Crossref
- Abstract
- Bromocriptine is an ergot alkaloid and dopamine D<sub>2</sub> receptor agonist used to treat Parkinson's disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 breast cancer cells. Bromocriptine strongly bound to NF-κB pathway proteins as shown by molecular docking and interacted more strongly with DNA-bound NF-κB than free NF-κB, indicating that bromocriptine may inhibit NF-κB binding to DNA. Furthermore, bromocriptine decreased NF-κB activity by a SEAP-driven NF-κB reporter cell assay. The expression of MDR-conferring ABC-transporters (ABCB1, ABCB5, ABCC1, and ABCG2) and other resistance-mediating factors (EGFR, mutated TP53, and IκB) did not correlate with cellular response to bromocriptine in a panel of 60 NCI cell lines. There was no correlation between cellular response to bromocriptine and anticancer drugs usually involved in MDR (e.g., anthracyclines, <i>Vinca</i> alkaloids, taxanes, epipodophyllotoxins, and others). COMPARE analysis of microarray-based mRNA expression in these cell lines revealed that genes from various functional groups such as ribosomal proteins, transcription, translation, DNA repair, DNA damage, protein folding, mitochondrial respiratory chain, and chemokines correlated with cellular response to bromocriptine. Our results indicate that bromocriptine inhibited drug-resistant tumor cells with different resistance mechanisms in a hormone-independent manner. As refractory and otherwise drug-resistant tumors represent a major challenge to successful cancer chemotherapy, bromocriptine may be considered for repurposing in cancer therapy.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Ean-Jeong Seo
- Yoshikazu Sugimoto
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.3389/fphar.2018.01030
- eISSN
- 1663-9812
- Externe Identifier
- PubMed Identifier: 30349477
- PubMed Central ID: PMC6187981
- Open access
- true
- ISSN
- 1663-9812
- Zeitschrift
- Frontiers in pharmacology
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2018
- Open access status
- Open Access
- Paginierung
- 1030
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2018
- Titel
- Repurposing of Bromocriptine for Cancer Therapy.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://www.frontiersin.org/articles/10.3389/fphar.2018.01030/pdf https://europepmc.org/articles/PMC6187981?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson's disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 breast cancer cells. Bromocriptine strongly bound to NF-κB pathway proteins as shown by molecular docking and interacted more strongly with DNA-bound NF-κB than free NF-κB, indicating that bromocriptine may inhibit NF-κB binding to DNA. Furthermore, bromocriptine decreased NF-κB activity by a SEAP-driven NF-κB reporter cell assay. The expression of MDR-conferring ABC-transporters (ABCB1, ABCB5, ABCC1, and ABCG2) and other resistance-mediating factors (EGFR, mutated TP53, and IκB) did not correlate with cellular response to bromocriptine in a panel of 60 NCI cell lines. There was no correlation between cellular response to bromocriptine and anticancer drugs usually involved in MDR (e.g., anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins, and others). COMPARE analysis of microarray-based mRNA expression in these cell lines revealed that genes from various functional groups such as ribosomal proteins, transcription, translation, DNA repair, DNA damage, protein folding, mitochondrial respiratory chain, and chemokines correlated with cellular response to bromocriptine. Our results indicate that bromocriptine inhibited drug-resistant tumor cells with different resistance mechanisms in a hormone-independent manner. As refractory and otherwise drug-resistant tumors represent a major challenge to successful cancer chemotherapy, bromocriptine may be considered for repurposing in cancer therapy.
- Date of acceptance
- 2018
- Autoren
- Ean-Jeong Seo
- Yoshikazu Sugimoto
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/30349477
- DOI
- 10.3389/fphar.2018.01030
- Externe Identifier
- PubMed Central ID: PMC6187981
- ISSN
- 1663-9812
- Zeitschrift
- Front Pharmacol
- Schlüsselwörter
- bromocriptine
- drug repurposing
- ergot alkaloids
- neoplasms
- pharmacogenomics
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 1030
- Datum der Veröffentlichung
- 2018
- Status
- Published online
- Titel
- Repurposing of Bromocriptine for Cancer Therapy.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Datenquelle: PubMed
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- Eigentum von