Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy
Identifieur interne : 000882 ( Main/Exploration ); précédent : 000881; suivant : 000883Dimethylfumarate 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
Affiliations:
- Allemagne, Suisse
- Canton de Zurich, District de Darmstadt, Hesse (Land)
- Francfort-sur-le-Main, Zurich
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Le document en format XML
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<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>
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<affiliations><list><country><li>Allemagne</li>
<li>Suisse</li>
</country>
<region><li>Canton de Zurich</li>
<li>District de Darmstadt</li>
<li>Hesse (Land)</li>
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<name sortKey="Hailemariam Jahn, Tsige" sort="Hailemariam Jahn, Tsige" uniqKey="Hailemariam Jahn T" first="Tsige" last="Hailemariam-Jahn">Tsige Hailemariam-Jahn</name>
<name sortKey="Kaufmann, Roland" sort="Kaufmann, Roland" uniqKey="Kaufmann R" first="Roland" last="Kaufmann">Roland Kaufmann</name>
<name sortKey="Kippenberger, Stefan" sort="Kippenberger, Stefan" uniqKey="Kippenberger S" first="Stefan" last="Kippenberger">Stefan Kippenberger</name>
<name sortKey="Meissner, Markus" sort="Meissner, Markus" uniqKey="Meissner M" first="Markus" last="Meissner">Markus Meissner</name>
<name sortKey="Zoller, Nadja" sort="Zoller, Nadja" uniqKey="Zoller N" first="Nadja" last="Zöller">Nadja Zöller</name>
</country>
<country name="Suisse"><region name="Canton de Zurich"><name sortKey="Balermpas, Panagiotis" sort="Balermpas, Panagiotis" uniqKey="Balermpas P" first="Panagiotis" last="Balermpas">Panagiotis Balermpas</name>
</region>
</country>
</tree>
</affiliations>
</record>
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