Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells
Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002,...
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| creator | Pruteanu, Lavinia-Lorena Kopanitsa, Liliya Módos, Dezso Kletnieks, Edgars Samarova, Elena Bender, Andreas Gomez, Leonardo Dario Bailey, David Stanley |
| description | Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease. |
| doi_str_mv | 10.1371/journal.pone.0239551 |
| format | Article |
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Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0239551</identifier><identifier>PMID: 32946518</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Agriculture ; Angiogenesis ; Antineoplastic agents ; Apoptosis ; Biology and Life Sciences ; Brain cancer ; Cancer ; Cancer therapies ; Care and treatment ; Carotenoids ; Cell cycle ; Cell proliferation ; Chemistry ; Complementarity ; Computer and Information Sciences ; Deoxyribonucleic acid ; Diet ; DNA ; DNA biosynthesis ; DNA damage ; Drug synergism ; Drug therapy ; Engineering and Technology ; Enzyme inhibitors ; Fucoxanthin ; Functional foods & nutraceuticals ; Gene expression ; Genetic aspects ; Genomes ; Glioblastoma ; Glioblastoma cells ; Glioblastomas ; Health aspects ; Informatics ; Kinases ; Lipid metabolism ; Lipids ; Medicine and Health Sciences ; Metabolism ; Natural products ; Pharmaceuticals ; Proteins ; Retina ; Retinoblastoma ; Supervision ; Transcription (Genetics) ; Tumors</subject><ispartof>PloS one, 2020-09, Vol.15 (9), p.e0239551-e0239551</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Pruteanu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Agriculture</subject><subject>Angiogenesis</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Brain cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Carotenoids</subject><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Chemistry</subject><subject>Complementarity</subject><subject>Computer and Information Sciences</subject><subject>Deoxyribonucleic acid</subject><subject>Diet</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA damage</subject><subject>Drug 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| ispartof | PloS one, 2020-09, Vol.15 (9), p.e0239551-e0239551 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2444086097 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Agriculture Angiogenesis Antineoplastic agents Apoptosis Biology and Life Sciences Brain cancer Cancer Cancer therapies Care and treatment Carotenoids Cell cycle Cell proliferation Chemistry Complementarity Computer and Information Sciences Deoxyribonucleic acid Diet DNA DNA biosynthesis DNA damage Drug synergism Drug therapy Engineering and Technology Enzyme inhibitors Fucoxanthin Functional foods & nutraceuticals Gene expression Genetic aspects Genomes Glioblastoma Glioblastoma cells Glioblastomas Health aspects Informatics Kinases Lipid metabolism Lipids Medicine and Health Sciences Metabolism Natural products Pharmaceuticals Proteins Retina Retinoblastoma Supervision Transcription (Genetics) Tumors |
| title | Transcriptomics predicts compound synergy in drug and natural product treated glioblastoma cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T10%3A05%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptomics%20predicts%20compound%20synergy%20in%20drug%20and%20natural%20product%20treated%20glioblastoma%20cells&rft.jtitle=PloS%20one&rft.au=Pruteanu,%20Lavinia-Lorena&rft.date=2020-09-18&rft.volume=15&rft.issue=9&rft.spage=e0239551&rft.epage=e0239551&rft.pages=e0239551-e0239551&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0239551&rft_dat=%3Cgale_plos_%3EA635828141%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2444086097&rft_id=info:pmid/32946518&rft_galeid=A635828141&rft_doaj_id=oai_doaj_org_article_815e5cc7e3e14633a1d89d0649c84216&rfr_iscdi=true |