PMID- 31661890
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20231213
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 11
DP  - 2019 Oct 28
TI  - Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for 
      Cell Cycle Arrest, Apoptosis and Autophagy.
LID - 10.3390/cells8111329 [doi]
LID - 1329
AB  - 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 
      antitumorigenic, 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.
FAU - Kaluzki, Irina
AU  - Kaluzki I
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. irina.kaluzki@kgu.de.
FAU - Hailemariam-Jahn, Tsige
AU  - Hailemariam-Jahn T
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. rita_th@web.de.
FAU - Doll, Monika
AU  - Doll M
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. monika.doll@kgu.de.
FAU - Kaufmann, Roland
AU  - Kaufmann R
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. roland.kaufmann@kgu.de.
FAU - Balermpas, Panagiotis
AU  - Balermpas P
AD  - Department of Radiation Oncology, Universitats Spital, 8091 Zurich, Switzerland. 
      panagiotis.balermpas@usz.ch.
FAU - Zoller, Nadja
AU  - Zoller N
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. nadja.zoeller@kgu.de.
FAU - Kippenberger, Stefan
AU  - Kippenberger S
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. kippenberger@em.uni-frankfurt.de.
FAU - Meissner, Markus
AU  - Meissner M
AD  - Department of Dermatology, Venereology and Allergology, Goethe-University, 60323 
      Frankfurt am Main, Germany. markus.meissner@kgu.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191028
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - FO2303MNI2 (Dimethyl Fumarate)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/*drug therapy/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Dimethyl Fumarate/metabolism/*pharmacology
MH  - Humans
MH  - Melanoma/metabolism
MH  - Skin Neoplasms/metabolism
MH  - Melanoma, Cutaneous Malignant
PMC - PMC6912700
OTO - NOTNLM
OT  - LC3 I/II
OT  - autophagy
OT  - caspase-8
OT  - cell cycle arrest
OT  - colorectal carcinoma
OT  - cyclin D1
OT  - dimethylfumarate
OT  - p21
OT  - p62
COIS- The authors declare no conflict of interest. The founding sponsors had no role in 
      the design of the study; in the collection, analyzes, or interpretation of data; 
      in the writing of the manuscript, and in the decision to publish the results.
EDAT- 2019/10/31 06:00
MHDA- 2020/07/09 06:00
PMCR- 2019/11/01
CRDT- 2019/10/31 06:00
PHST- 2019/08/09 00:00 [received]
PHST- 2019/10/18 00:00 [revised]
PHST- 2019/10/25 00:00 [accepted]
PHST- 2019/10/31 06:00 [entrez]
PHST- 2019/10/31 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - cells8111329 [pii]
AID - cells-08-01329 [pii]
AID - 10.3390/cells8111329 [doi]
PST - epublish
SO  - Cells. 2019 Oct 28;8(11):1329. doi: 10.3390/cells8111329.