Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy
Identifieur interne : 000477 ( Pmc/Curation ); précédent : 000476; suivant : 000478Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy
Auteurs : Irina Kaluzki [Allemagne] ; Tsige Hailemariam-Jahn [Allemagne] ; Monika Doll [Allemagne] ; Roland Kaufmann [Allemagne] ; Panagiotis Balermpas [Suisse] ; Nadja Zöller [Allemagne] ; Stefan Kippenberger [Allemagne] ; Markus Meissner [Allemagne]Source :
- Cells [ 2073-4409 ] ; 2019.
Abstract
Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.
Url:
DOI: 10.3390/cells8111329
PubMed: 31661890
PubMed Central: 6912700
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000477
Links to Exploration step
PMC:6912700Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy</title><author><name sortKey="Kaluzki, Irina" sort="Kaluzki, Irina" uniqKey="Kaluzki I" first="Irina" last="Kaluzki">Irina Kaluzki</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Hailemariam Jahn, Tsige" sort="Hailemariam Jahn, Tsige" uniqKey="Hailemariam Jahn T" first="Tsige" last="Hailemariam-Jahn">Tsige Hailemariam-Jahn</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Doll, Monika" sort="Doll, Monika" uniqKey="Doll M" first="Monika" last="Doll">Monika Doll</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Kaufmann, Roland" sort="Kaufmann, Roland" uniqKey="Kaufmann R" first="Roland" last="Kaufmann">Roland Kaufmann</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Balermpas, Panagiotis" sort="Balermpas, Panagiotis" uniqKey="Balermpas P" first="Panagiotis" last="Balermpas">Panagiotis Balermpas</name><affiliation wicri:level="1"><nlm:aff id="af2-cells-08-01329">Department of Radiation Oncology, UniversitätsSpital, 8091 Zürich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Radiation Oncology, UniversitätsSpital, 8091 Zürich</wicri:regionArea></affiliation></author><author><name sortKey="Zoller, Nadja" sort="Zoller, Nadja" uniqKey="Zoller N" first="Nadja" last="Zöller">Nadja Zöller</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Kippenberger, Stefan" sort="Kippenberger, Stefan" uniqKey="Kippenberger S" first="Stefan" last="Kippenberger">Stefan Kippenberger</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Meissner, Markus" sort="Meissner, Markus" uniqKey="Meissner M" first="Markus" last="Meissner">Markus Meissner</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31661890</idno><idno type="pmc">6912700</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912700</idno><idno type="RBID">PMC:6912700</idno><idno type="doi">10.3390/cells8111329</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000477</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000477</idno><idno type="wicri:Area/Pmc/Curation">000477</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000477</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy</title><author><name sortKey="Kaluzki, Irina" sort="Kaluzki, Irina" uniqKey="Kaluzki I" first="Irina" last="Kaluzki">Irina Kaluzki</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Hailemariam Jahn, Tsige" sort="Hailemariam Jahn, Tsige" uniqKey="Hailemariam Jahn T" first="Tsige" last="Hailemariam-Jahn">Tsige Hailemariam-Jahn</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Doll, Monika" sort="Doll, Monika" uniqKey="Doll M" first="Monika" last="Doll">Monika Doll</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Kaufmann, Roland" sort="Kaufmann, Roland" uniqKey="Kaufmann R" first="Roland" last="Kaufmann">Roland Kaufmann</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Balermpas, Panagiotis" sort="Balermpas, Panagiotis" uniqKey="Balermpas P" first="Panagiotis" last="Balermpas">Panagiotis Balermpas</name><affiliation wicri:level="1"><nlm:aff id="af2-cells-08-01329">Department of Radiation Oncology, UniversitätsSpital, 8091 Zürich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Radiation Oncology, UniversitätsSpital, 8091 Zürich</wicri:regionArea></affiliation></author><author><name sortKey="Zoller, Nadja" sort="Zoller, Nadja" uniqKey="Zoller N" first="Nadja" last="Zöller">Nadja Zöller</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Kippenberger, Stefan" sort="Kippenberger, Stefan" uniqKey="Kippenberger S" first="Stefan" last="Kippenberger">Stefan Kippenberger</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author><author><name sortKey="Meissner, Markus" sort="Meissner, Markus" uniqKey="Meissner M" first="Markus" last="Meissner">Markus Meissner</name><affiliation wicri:level="1"><nlm:aff id="af1-cells-08-01329">Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cells</title><idno type="eISSN">2073-4409</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author><author><name sortKey="Siegel, R L" uniqKey="Siegel R">R.L. Siegel</name></author><author><name sortKey="Torre, L A" uniqKey="Torre L">L.A. Torre</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A. Jemal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Cutsem, E" uniqKey="Van Cutsem E">E. Van Cutsem</name></author><author><name sortKey="Cervantes, A" uniqKey="Cervantes A">A. Cervantes</name></author><author><name sortKey="Adam, R" uniqKey="Adam R">R. Adam</name></author><author><name sortKey="Sobrero, A" uniqKey="Sobrero A">A. Sobrero</name></author><author><name sortKey="Van Krieken, J H" uniqKey="Van Krieken J">J.H. Van Krieken</name></author><author><name sortKey="Aderka, D" uniqKey="Aderka D">D. Aderka</name></author><author><name sortKey="Aranda Aguilar, E" uniqKey="Aranda Aguilar E">E. Aranda Aguilar</name></author><author><name sortKey="Bardelli, A" uniqKey="Bardelli A">A. Bardelli</name></author><author><name sortKey="Benson, A" uniqKey="Benson A">A. Benson</name></author><author><name sortKey="Bodoky, G" uniqKey="Bodoky G">G. Bodoky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Werdenberg, D" uniqKey="Werdenberg D">D. Werdenberg</name></author><author><name sortKey="Joshi, R" uniqKey="Joshi R">R. Joshi</name></author><author><name sortKey="Wolffram, S" uniqKey="Wolffram S">S. Wolffram</name></author><author><name sortKey="Merkle, H P" uniqKey="Merkle H">H.P. Merkle</name></author><author><name sortKey="Langguth, P" uniqKey="Langguth P">P. Langguth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaluzki, I" uniqKey="Kaluzki I">I. Kaluzki</name></author><author><name sortKey="Hrgovic, I" uniqKey="Hrgovic I">I. Hrgovic</name></author><author><name sortKey="Hailemariam Jahn, T" uniqKey="Hailemariam Jahn T">T. Hailemariam-Jahn</name></author><author><name sortKey="Doll, M" uniqKey="Doll M">M. Doll</name></author><author><name sortKey="Kleemann, J" uniqKey="Kleemann J">J. Kleemann</name></author><author><name sortKey="Valesky, E M" uniqKey="Valesky E">E.M. Valesky</name></author><author><name sortKey="Kippenberger, S" uniqKey="Kippenberger S">S. Kippenberger</name></author><author><name sortKey="Kaufmann, R" uniqKey="Kaufmann R">R. Kaufmann</name></author><author><name sortKey="Zoeller, N" uniqKey="Zoeller N">N. Zoeller</name></author><author><name sortKey="Meissner, M" uniqKey="Meissner M">M. Meissner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirlin, W G" uniqKey="Kirlin W">W.G. Kirlin</name></author><author><name sortKey="Cai, J" uniqKey="Cai J">J. Cai</name></author><author><name sortKey="Delong, M J" uniqKey="Delong M">M.J. Delong</name></author><author><name sortKey="Patten, E J" uniqKey="Patten E">E.J. Patten</name></author><author><name sortKey="Jones, D P" uniqKey="Jones D">D.P. Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, X" uniqKey="Xie X">X. Xie</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y. Zhao</name></author><author><name sortKey="Ma, C Y" uniqKey="Ma C">C.-Y. Ma</name></author><author><name sortKey="Xu, X M" uniqKey="Xu X">X.-M. Xu</name></author><author><name sortKey="Zhang, Y Q" uniqKey="Zhang Y">Y.-Q. Zhang</name></author><author><name sortKey="Wang, C G" uniqKey="Wang C">C.-G. Wang</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J. Jin</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Gao, J L" uniqKey="Gao J">J.-L. Gao</name></author><author><name sortKey="Li, N" uniqKey="Li N">N. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N. Mizushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Begleiter, A" uniqKey="Begleiter A">A. Begleiter</name></author><author><name sortKey="Sivananthan, K" uniqKey="Sivananthan K">K. Sivananthan</name></author><author><name sortKey="Curphey, T J" uniqKey="Curphey T">T.J. Curphey</name></author><author><name sortKey="Bird, R P" uniqKey="Bird R">R.P. Bird</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vego, H" uniqKey="Vego H">H. Vego</name></author><author><name sortKey="Sand, K L" uniqKey="Sand K">K.L. Sand</name></author><author><name sortKey="H Glund, R A" uniqKey="H Glund R">R.A. Høglund</name></author><author><name sortKey="Fallang, L E" uniqKey="Fallang L">L.E. Fallang</name></author><author><name sortKey="Gundersen, G" uniqKey="Gundersen G">G. Gundersen</name></author><author><name sortKey="Holm Y, T" uniqKey="Holm Y T">T. Holmøy</name></author><author><name sortKey="Maghazachi, A A" uniqKey="Maghazachi A">A.A. Maghazachi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valesky, E M" uniqKey="Valesky E">E.M. Valesky</name></author><author><name sortKey="Hrgovic, I" uniqKey="Hrgovic I">I. Hrgovic</name></author><author><name sortKey="Doll, M" uniqKey="Doll M">M. Doll</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Pinter, A" uniqKey="Pinter A">A. Pintér</name></author><author><name sortKey="Kleemann, J" uniqKey="Kleemann J">J. Kleemann</name></author><author><name sortKey="Kaufmann, R" uniqKey="Kaufmann R">R. Kaufmann</name></author><author><name sortKey="Kippenberger, S" uniqKey="Kippenberger S">S. Kippenberger</name></author><author><name sortKey="Meissner, M" uniqKey="Meissner M">M. Meissner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meissner, M" uniqKey="Meissner M">M. Meissner</name></author><author><name sortKey="Doll, M" uniqKey="Doll M">M. Doll</name></author><author><name sortKey="Hrgovic, I" uniqKey="Hrgovic I">I. Hrgovic</name></author><author><name sortKey="Reichenbach, G" uniqKey="Reichenbach G">G. Reichenbach</name></author><author><name sortKey="Konig, V" uniqKey="Konig V">V. König</name></author><author><name sortKey="Hailemariam Jahn, T" uniqKey="Hailemariam Jahn T">T. Hailemariam-Jahn</name></author><author><name sortKey="Gille, J" uniqKey="Gille J">J. Gille</name></author><author><name sortKey="Kaufmann, R" uniqKey="Kaufmann R">R. Kaufmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loewe, R" uniqKey="Loewe R">R. Loewe</name></author><author><name sortKey="Holnthoner, W" uniqKey="Holnthoner W">W. Holnthoner</name></author><author><name sortKey="Groger, M" uniqKey="Groger M">M. Gröger</name></author><author><name sortKey="Pillinger, M" uniqKey="Pillinger M">M. Pillinger</name></author><author><name sortKey="Gruber, F" uniqKey="Gruber F">F. Gruber</name></author><author><name sortKey="Mechtcheriakova, D" uniqKey="Mechtcheriakova D">D. Mechtcheriakova</name></author><author><name sortKey="Hofer, E" uniqKey="Hofer E">E. Hofer</name></author><author><name sortKey="Wolff, K" uniqKey="Wolff K">K. Wolff</name></author><author><name sortKey="Petzelbauer, P" uniqKey="Petzelbauer P">P. Petzelbauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerhardt, S" uniqKey="Gerhardt S">S. Gerhardt</name></author><author><name sortKey="Konig, V" uniqKey="Konig V">V. König</name></author><author><name sortKey="Doll, M" uniqKey="Doll M">M. Doll</name></author><author><name sortKey="Hailemariam Jahn, T" uniqKey="Hailemariam Jahn T">T. Hailemariam-Jahn</name></author><author><name sortKey="Hrgovic, I" uniqKey="Hrgovic I">I. Hrgovic</name></author><author><name sortKey="Zoller, N" uniqKey="Zoller N">N. Zöller</name></author><author><name sortKey="Kaufmann, R" uniqKey="Kaufmann R">R. Kaufmann</name></author><author><name sortKey="Kippenberger, S" uniqKey="Kippenberger S">S. Kippenberger</name></author><author><name sortKey="Meissner, M" uniqKey="Meissner M">M. Meissner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamazoe, Y" uniqKey="Yamazoe Y">Y. Yamazoe</name></author><author><name sortKey="Tsubaki, M" uniqKey="Tsubaki M">M. Tsubaki</name></author><author><name sortKey="Matsuoka, H" uniqKey="Matsuoka H">H. Matsuoka</name></author><author><name sortKey="Satou, T" uniqKey="Satou T">T. Satou</name></author><author><name sortKey="Itoh, T" uniqKey="Itoh T">T. Itoh</name></author><author><name sortKey="Kusunoki, T" uniqKey="Kusunoki T">T. Kusunoki</name></author><author><name sortKey="Kidera, Y" uniqKey="Kidera Y">Y. Kidera</name></author><author><name sortKey="Tanimori, Y" uniqKey="Tanimori Y">Y. Tanimori</name></author><author><name sortKey="Shoji, K" uniqKey="Shoji K">K. Shoji</name></author><author><name sortKey="Nakamura, H" uniqKey="Nakamura H">H. Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oh, C J" uniqKey="Oh C">C.J. Oh</name></author><author><name sortKey="Park, S" uniqKey="Park S">S. Park</name></author><author><name sortKey="Kim, J Y" uniqKey="Kim J">J.-Y. Kim</name></author><author><name sortKey="Kim, H J" uniqKey="Kim H">H.-J. Kim</name></author><author><name sortKey="Jeoung, N H" uniqKey="Jeoung N">N.H. Jeoung</name></author><author><name sortKey="Choi, Y K" uniqKey="Choi Y">Y.-K. Choi</name></author><author><name sortKey="Go, Y" uniqKey="Go Y">Y. Go</name></author><author><name sortKey="Park, K G" uniqKey="Park K">K.-G. Park</name></author><author><name sortKey="Lee, I K" uniqKey="Lee I">I.-K. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Odom, R Y" uniqKey="Odom R">R.Y. Odom</name></author><author><name sortKey="Dansby, M Y" uniqKey="Dansby M">M.Y. Dansby</name></author><author><name sortKey="Rollins Hairston, A M" uniqKey="Rollins Hairston A">A.M. Rollins-Hairston</name></author><author><name sortKey="Jackson, K M" uniqKey="Jackson K">K.M. Jackson</name></author><author><name sortKey="Kirlin, W G" uniqKey="Kirlin W">W.G. Kirlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, Z G" uniqKey="Ma Z">Z.-G. Ma</name></author><author><name sortKey="Ma, R" uniqKey="Ma R">R. Ma</name></author><author><name sortKey="Xiao, X L" uniqKey="Xiao X">X.-L. Xiao</name></author><author><name sortKey="Zhang, Y H" uniqKey="Zhang Y">Y.-H. Zhang</name></author><author><name sortKey="Zhang, X Z" uniqKey="Zhang X">X.-Z. Zhang</name></author><author><name sortKey="Hu, N" uniqKey="Hu N">N. Hu</name></author><author><name sortKey="Gao, J L" uniqKey="Gao J">J.-L. Gao</name></author><author><name sortKey="Zheng, Y F" uniqKey="Zheng Y">Y.-F. Zheng</name></author><author><name sortKey="Dong, D L" uniqKey="Dong D">D.-L. Dong</name></author><author><name sortKey="Sun, Z J" uniqKey="Sun Z">Z.-J. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, H J" uniqKey="Kang H">H.-J. Kang</name></author><author><name sortKey="Seo, H A" uniqKey="Seo H">H.-A. Seo</name></author><author><name sortKey="Go, Y" uniqKey="Go Y">Y. Go</name></author><author><name sortKey="Oh, C J" uniqKey="Oh C">C.J. Oh</name></author><author><name sortKey="Jeoung, N H" uniqKey="Jeoung N">N.H. Jeoung</name></author><author><name sortKey="Park, K G" uniqKey="Park K">K.-G. Park</name></author><author><name sortKey="Lee, I K" uniqKey="Lee I">I.-K. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singh, P" uniqKey="Singh P">P. Singh</name></author><author><name sortKey="Blatt, A" uniqKey="Blatt A">A. Blatt</name></author><author><name sortKey="Feld, S" uniqKey="Feld S">S. Feld</name></author><author><name sortKey="Zohar, Y" uniqKey="Zohar Y">Y. Zohar</name></author><author><name sortKey="Saadi, E" uniqKey="Saadi E">E. Saadi</name></author><author><name sortKey="Barki Harrington, L" uniqKey="Barki Harrington L">L. Barki-Harrington</name></author><author><name sortKey="Hammond, E" uniqKey="Hammond E">E. Hammond</name></author><author><name sortKey="Ilan, N" uniqKey="Ilan N">N. Ilan</name></author><author><name sortKey="Vlodavsky, I" uniqKey="Vlodavsky I">I. Vlodavsky</name></author><author><name sortKey="Chowers, Y" uniqKey="Chowers Y">Y. Chowers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Afrin, S" uniqKey="Afrin S">S. Afrin</name></author><author><name sortKey="Giampieri, F" uniqKey="Giampieri F">F. Giampieri</name></author><author><name sortKey="Gasparrini, M" uniqKey="Gasparrini M">M. Gasparrini</name></author><author><name sortKey="Forbes Hernandez, T Y" uniqKey="Forbes Hernandez T">T.Y. Forbes-Hernández</name></author><author><name sortKey="Cianciosi, D" uniqKey="Cianciosi D">D. Cianciosi</name></author><author><name sortKey="Rodriguez, P R" uniqKey="Rodriguez P">P.R. Rodríguez</name></author><author><name sortKey="Amici, A" uniqKey="Amici A">A. Amici</name></author><author><name sortKey="Quiles, J L" uniqKey="Quiles J">J.L. Quiles</name></author><author><name sortKey="Battino, M" uniqKey="Battino M">M. Battino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singh, S K" uniqKey="Singh S">S.K. Singh</name></author><author><name sortKey="Banerjee, S" uniqKey="Banerjee S">S. Banerjee</name></author><author><name sortKey="Acosta, E P" uniqKey="Acosta E">E.P. Acosta</name></author><author><name sortKey="Lillard, J W" uniqKey="Lillard J">J.W. Lillard</name></author><author><name sortKey="Singh, R" uniqKey="Singh R">R. Singh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rezaei, P F" uniqKey="Rezaei P">P.F. Rezaei</name></author><author><name sortKey="Fouladdel, S" uniqKey="Fouladdel S">S. Fouladdel</name></author><author><name sortKey="Ghaffari, S M" uniqKey="Ghaffari S">S.M. Ghaffari</name></author><author><name sortKey="Amin, G" uniqKey="Amin G">G. Amin</name></author><author><name sortKey="Azizi, E" uniqKey="Azizi E">E. Azizi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loewe, R" uniqKey="Loewe R">R. Loewe</name></author><author><name sortKey="Valero, T" uniqKey="Valero T">T. Valero</name></author><author><name sortKey="Kremling, S" uniqKey="Kremling S">S. Kremling</name></author><author><name sortKey="Pratscher, B" uniqKey="Pratscher B">B. Pratscher</name></author><author><name sortKey="Kunstfeld, R" uniqKey="Kunstfeld R">R. Kunstfeld</name></author><author><name sortKey="Pehamberger, H" uniqKey="Pehamberger H">H. Pehamberger</name></author><author><name sortKey="Petzelbauer, P" uniqKey="Petzelbauer P">P. Petzelbauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsubaki, M" uniqKey="Tsubaki M">M. Tsubaki</name></author><author><name sortKey="Ogawa, N" uniqKey="Ogawa N">N. Ogawa</name></author><author><name sortKey="Takeda, T" uniqKey="Takeda T">T. Takeda</name></author><author><name sortKey="Sakamoto, K" uniqKey="Sakamoto K">K. Sakamoto</name></author><author><name sortKey="Shimaoka, H" uniqKey="Shimaoka H">H. Shimaoka</name></author><author><name sortKey="Fujita, A" uniqKey="Fujita A">A. Fujita</name></author><author><name sortKey="Itoh, T" uniqKey="Itoh T">T. Itoh</name></author><author><name sortKey="Imano, M" uniqKey="Imano M">M. Imano</name></author><author><name sortKey="Satou, T" uniqKey="Satou T">T. Satou</name></author><author><name sortKey="Nishida, S" uniqKey="Nishida S">S. Nishida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, K" uniqKey="Ma K">K. Ma</name></author><author><name sortKey="Zhang, C" uniqKey="Zhang C">C. Zhang</name></author><author><name sortKey="Huang, M Y" uniqKey="Huang M">M.-Y. Huang</name></author><author><name sortKey="Guo, Y X" uniqKey="Guo Y">Y.-X. Guo</name></author><author><name sortKey="Hu, G Q" uniqKey="Hu G">G.-Q. Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H. Xu</name></author><author><name sortKey="Yu, X" uniqKey="Yu X">X. Yu</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Zhu, X" uniqKey="Zhu X">X. Zhu</name></author><author><name sortKey="Xu, X" uniqKey="Xu X">X. Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Son, Y" uniqKey="Son Y">Y. Son</name></author><author><name sortKey="An, Y" uniqKey="An Y">Y. An</name></author><author><name sortKey="Jung, J" uniqKey="Jung J">J. Jung</name></author><author><name sortKey="Shin, S" uniqKey="Shin S">S. Shin</name></author><author><name sortKey="Park, I" uniqKey="Park I">I. Park</name></author><author><name sortKey="Gwak, J" uniqKey="Gwak J">J. Gwak</name></author><author><name sortKey="Ju, B G" uniqKey="Ju B">B.G. Ju</name></author><author><name sortKey="Chung, Y" uniqKey="Chung Y">Y. Chung</name></author><author><name sortKey="Na, M" uniqKey="Na M">M. Na</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S. Oh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, G Y" uniqKey="Gao G">G.-Y. Gao</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J. Ma</name></author><author><name sortKey="Lu, P" uniqKey="Lu P">P. Lu</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Chang, C" uniqKey="Chang C">C. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Ye, Z" uniqKey="Ye Z">Z. Ye</name></author><author><name sortKey="Li, J C" uniqKey="Li J">J.C. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Kuramitsu, Y" uniqKey="Kuramitsu Y">Y. Kuramitsu</name></author><author><name sortKey="Baron, B" uniqKey="Baron B">B. Baron</name></author><author><name sortKey="Kitagawa, T" uniqKey="Kitagawa T">T. Kitagawa</name></author><author><name sortKey="Tokuda, K" uniqKey="Tokuda K">K. Tokuda</name></author><author><name sortKey="Akada, J" uniqKey="Akada J">J. Akada</name></author><author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K. Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, J D" uniqKey="Fan J">J.D. Fan</name></author><author><name sortKey="Lei, P J" uniqKey="Lei P">P.J. Lei</name></author><author><name sortKey="Zheng, J Y" uniqKey="Zheng J">J.Y. Zheng</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Li, S" uniqKey="Li S">S. Li</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="He, Y L" uniqKey="He Y">Y.L. He</name></author><author><name sortKey="Wang, Z N" uniqKey="Wang Z">Z.N. Wang</name></author><author><name sortKey="Wei, G" uniqKey="Wei G">G. Wei</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Di Giacomo, V" uniqKey="Di Giacomo V">V. Di Giacomo</name></author><author><name sortKey="Di Valerio, V" uniqKey="Di Valerio V">V. Di Valerio</name></author><author><name sortKey="Rapino, M" uniqKey="Rapino M">M. Rapino</name></author><author><name sortKey="Bosco, D" uniqKey="Bosco D">D. Bosco</name></author><author><name sortKey="Cacciatore, I" uniqKey="Cacciatore I">I. Cacciatore</name></author><author><name sortKey="Ciulla, M" uniqKey="Ciulla M">M. Ciulla</name></author><author><name sortKey="Marrazzo, A" uniqKey="Marrazzo A">A. Marrazzo</name></author><author><name sortKey="Fiorito, J" uniqKey="Fiorito J">J. Fiorito</name></author><author><name sortKey="Di Stefano, A" uniqKey="Di Stefano A">A. Di Stefano</name></author><author><name sortKey="Cataldi, A" uniqKey="Cataldi A">A. Cataldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanot, M" uniqKey="Hanot M">M. Hanot</name></author><author><name sortKey="Boivin, A" uniqKey="Boivin A">A. Boivin</name></author><author><name sortKey="Malesys, C" uniqKey="Malesys C">C. Malésys</name></author><author><name sortKey="Beuve, M" uniqKey="Beuve M">M. Beuve</name></author><author><name sortKey="Colliaux, A" uniqKey="Colliaux A">A. Colliaux</name></author><author><name sortKey="Foray, N" uniqKey="Foray N">N. Foray</name></author><author><name sortKey="Douki, T" uniqKey="Douki T">T. Douki</name></author><author><name sortKey="Ardail, D" uniqKey="Ardail D">D. Ardail</name></author><author><name sortKey="Rodriguez Lafrasse, C" uniqKey="Rodriguez Lafrasse C">C. Rodriguez-Lafrasse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boivin, A" uniqKey="Boivin A">A. Boivin</name></author><author><name sortKey="Hanot, M" uniqKey="Hanot M">M. Hanot</name></author><author><name sortKey="Malesys, C" uniqKey="Malesys C">C. Malésys</name></author><author><name sortKey="Maalouf, M" uniqKey="Maalouf M">M. Maalouf</name></author><author><name sortKey="Rousson, R" uniqKey="Rousson R">R. Rousson</name></author><author><name sortKey="Rodriguez Lafrasse, C" uniqKey="Rodriguez Lafrasse C">C. Rodriguez-Lafrasse</name></author><author><name sortKey="Ardail, D" uniqKey="Ardail D">D. Ardail</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Booth, L" uniqKey="Booth L">L. Booth</name></author><author><name sortKey="Cruickshanks, N" uniqKey="Cruickshanks N">N. Cruickshanks</name></author><author><name sortKey="Tavallai, S" uniqKey="Tavallai S">S. Tavallai</name></author><author><name sortKey="Roberts, J L" uniqKey="Roberts J">J.L. Roberts</name></author><author><name sortKey="Peery, M" uniqKey="Peery M">M. Peery</name></author><author><name sortKey="Poklepovic, A" uniqKey="Poklepovic A">A. Poklepovic</name></author><author><name sortKey="Dent, P" uniqKey="Dent P">P. Dent</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Cells</journal-id><journal-id journal-id-type="iso-abbrev">Cells</journal-id><journal-id journal-id-type="publisher-id">cells</journal-id><journal-title-group><journal-title>Cells</journal-title></journal-title-group><issn pub-type="epub">2073-4409</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31661890</article-id><article-id pub-id-type="pmc">6912700</article-id><article-id pub-id-type="doi">10.3390/cells8111329</article-id><article-id pub-id-type="publisher-id">cells-08-01329</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kaluzki</surname><given-names>Irina</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><name><surname>Hailemariam-Jahn</surname><given-names>Tsige</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><name><surname>Doll</surname><given-names>Monika</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><name><surname>Kaufmann</surname><given-names>Roland</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-5261-6446</contrib-id><name><surname>Balermpas</surname><given-names>Panagiotis</given-names></name><xref ref-type="aff" rid="af2-cells-08-01329">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-2438-2747</contrib-id><name><surname>Zöller</surname><given-names>Nadja</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><name><surname>Kippenberger</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-5630-587X</contrib-id><name><surname>Meissner</surname><given-names>Markus</given-names></name><xref ref-type="aff" rid="af1-cells-08-01329">1</xref><xref rid="c1-cells-08-01329" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cells-08-01329"><label>1</label>Department of Dermatology, Venereology and Allergology, Goethe-University, 60438 Frankfurt am Main, Germany</aff><aff id="af2-cells-08-01329"><label>2</label>Department of Radiation Oncology, UniversitätsSpital, 8091 Zürich, Switzerland</aff><author-notes><corresp id="c1-cells-08-01329"><label>*</label>Correspondence: <email>markus.meissner@kgu.de</email></corresp></author-notes><pub-date pub-type="epub"><day>28</day><month>10</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>11</month><year>2019</year></pub-date><volume>8</volume><issue>11</issue><elocation-id>1329</elocation-id><history><date date-type="received"><day>09</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>25</day><month>10</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.</p></abstract><kwd-group><kwd>dimethylfumarate</kwd><kwd>colorectal carcinoma</kwd><kwd>p21</kwd><kwd>cell cycle arrest</kwd><kwd>cyclin D1</kwd><kwd>p62</kwd><kwd>LC3 I/II</kwd><kwd>caspase-8</kwd><kwd>autophagy</kwd></kwd-group></article-meta></front><floats-group><fig id="cells-08-01329-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Chemical structure of Dimethylfumarate performed with Jmol (Jmol: an open-source Java viewer for chemical structures in 3D. <uri xlink:href="http://www.jmol.org/">http://www.jmol.org/</uri>).</p></caption><graphic xlink:href="cells-08-01329-g001"></graphic></fig><fig id="cells-08-01329-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>DMF suppresses colon carcinoma cell proliferation but does not display cytotoxic effects. (<bold>a</bold>,<bold>b</bold>) proliferation assay: HT-29 and T84 were treated for 24 h with the indicated concentrations of DMF. Dimethylsulfoxide (DMSO) 0.2% solvent served as control; (<bold>c</bold>,<bold>d</bold>) proliferation assay: HT-29 and T84 were treated with 100 µM DMF for the indicated time. DMSO 0.2% solvent served as control; (<bold>e</bold>,<bold>f</bold>) cytotoxicity-assay: HT-29 and T84 were treated for 24 h with the indicated concentrations of DMF. DMSO 0.2% solvent served as negative control, Triton X as a positive control. Mean values from at least three independent experiments are shown as mean ± SD. * <italic>p</italic> < 0.05: significant.</p></caption><graphic xlink:href="cells-08-01329-g002a"></graphic><graphic xlink:href="cells-08-01329-g002b"></graphic></fig><fig id="cells-08-01329-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>DMF induces G0/G1 arrest in HT-29 and increases the sub-G0/G1 phase in T84. Analysis of cell cycle distribution by FACS using propidium iodide-stained colon carcinoma cell lines (<bold>a</bold>) HT-29 treated with 100 µM DMF for 24 h; (<bold>b</bold>) T84 were treated with 100 µM DMF for 24 h. Positive control: Staurosporine 1 µM; Negative control: DMSO 0.2%. Data displayed are the mean values of at least three independent experiments and results are shown as mean ± SD. * <italic>p</italic> < 0.05: significant.</p></caption><graphic xlink:href="cells-08-01329-g003"></graphic></fig><fig id="cells-08-01329-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>DMF induces p21 in both cell lines and p53 in HT-29 and suppresses CDK4 and cyclin D1 protein expression only in HT-29 cells. Representative Western blot analyses of (<bold>a</bold>,<bold>b</bold>) HT-29 treated for 24 h with DMF in the indicated concentrations and (<bold>c</bold>) T84 cells treated for 24 h with DMF in the indicated concentrations. DMSO 0.2% served as a solvent control. Comparable results were obtained from at least three independent experiments.</p></caption><graphic xlink:href="cells-08-01329-g004"></graphic></fig><fig id="cells-08-01329-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>DMF induces apoptosis and caspase-3/7 activation in T84 but not HT-29 cells. Analysis of apoptosis using the Cell Death Detection Kit. (<bold>a</bold>) HT-29 cells were treated for 24 h with DMF at the indicated concentrations; (<bold>b</bold>) T84 cells were treated for 24 h with DMF at the indicated concentrations. Analysis of caspase-3/7 activity; (<bold>c</bold>) HT-29 cells were treated for 24 h with DMF at the indicated concentrations; and (<bold>d</bold>) T84 cells were treated for 24 h with DMF at the indicated concentrations. Mean values from at least three independent experiments are shown as mean ± SD. * <italic>p</italic> < 0.05: significant. As a positive control, staurosporine (SSP) 1 µM was used. DMSO 0.2% served as a solvent control.</p></caption><graphic xlink:href="cells-08-01329-g005"></graphic></fig><fig id="cells-08-01329-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>DMF induces autophagy in HT-29 and T84 colon carcinoma cell lines. (<bold>a</bold>) representative immunofluorosecence of autophagy using Cyto-ID<sup>®</sup> assay. Cells were treated with DMF (100 µM) or solvent for 24 h. As a positive control Rapamycin (500 nM) + Chloroquine (10 µM) were used; (<bold>b</bold>) representative Western blot analyzes of LC3 A/B. Cells were treated for 24 h with vehicle or DMF for the indicated concentrations. The two arrows mark the type I (upper arrow) and type II (lower arrow) LC3A/B; (<bold>c</bold>) representative Western blot analysis from different autophagy associated proteins. Cells were treated for 24 h with vehicle or DMF for the indicated concentrations. Comparable results were obtained from at least three independent experiments.</p></caption><graphic xlink:href="cells-08-01329-g006"></graphic></fig><fig id="cells-08-01329-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Combinational treatment with DMF and radiation or oxaliplatin. Proliferation assay for the DMF/radiation treatment (<bold>a</bold>) HT-29 and (<bold>b</bold>) T84 cell lines. DMF pretreated cells (3 h) were exposed to 0 Gy vs. 2 Gy and incubated for additional 21 h for an overall treatment timed of 24 h. Proliferation assay for DMF/oxaliplatin treatment in (<bold>c</bold>) HT-29 and (<bold>d</bold>) T84 cell lines. Oxaliplatin was added 2 h after pre-incubation with DMF or solvent, respectively, at indicated concentrations for another 22 h. Mean values from at least three independent experiments are shown as mean ± SD. <italic>p</italic> < 0.05: significant. * significant compared to untreated control. ** significant compared to single treatments and untreated control.</p></caption><graphic xlink:href="cells-08-01329-g007"></graphic></fig><fig id="cells-08-01329-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Possible DMF dependent way of regulation in colon carcinoma cell lines.</p></caption><graphic xlink:href="cells-08-01329-g008"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000477 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000477 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:6912700
|texte= Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:31661890" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |