Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation

Wim Wätjen, Abdessamad Debbab, Anke Hohlfeld, Yvonni Chovolou, Andreas Kampkötter, Ru Angelie Edrada, Rainer Ebel, Abdelhak Hakiki, Mahjouba Mosaddak, Frank Totzke, Michael H G Kubbutat, Peter Proksch

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Abstract

Enniatins are mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible anticancer agents. We investigated toxic effects of enniatins A1, B and B1 isolated from Fusarium tricinctum on different cancer cell lines. The enniatins showed moderate activity in HepG2 and C6 cells (EC(50)-values approximately 10-25 microM), but were highly toxic in H4IIE cells (EC(50)-values approximately 1-2.5 microM). In H4IIE cells, all enniatins increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Enniatin A1, enniatin B1, and, to a lesser extent, also enniatin B decreased the activation of extracellular regulated protein kinase (ERK) (p44/p42), a mitogen-activated protein kinase which is associated with cell proliferation. Furthermore, enniatins A1 and B1, but not enniatin B were able to inhibit moderately tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation. Screening of 24 additional protein kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) showed no inhibitory activity of enniatins. We conclude that enniatins A1 and B1 and, to a lesser extent, enniatin B may possess anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Further analysis of these substances is necessary to analyse their usefulness for cancer therapy.
Original languageEnglish
Pages (from-to)431-440
Number of pages10
JournalMolecular Nutrition & Food Research
Volume53
Issue number4
Early online date8 Dec 2008
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Fusarium tricinctum
Fusarium
hepatoma
protein kinases
Protein Kinases
cell death
Hepatocellular Carcinoma
phosphorylation
Cell Death
Phosphorylation
cell proliferation
transcription factor NF-kappa B
antineoplastic agents
anticarcinogenic activity
cells
caspase-3
angiogenesis
mitogen-activated protein kinase
metastasis
mycotoxins

Keywords

  • apoptosis
  • cytotoxicity
  • enniatins
  • ERK
  • NF-κB

Cite this

Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. / Wätjen, Wim; Debbab, Abdessamad; Hohlfeld, Anke; Chovolou, Yvonni; Kampkötter, Andreas; Edrada, Ru Angelie; Ebel, Rainer; Hakiki, Abdelhak; Mosaddak, Mahjouba; Totzke, Frank; Kubbutat, Michael H G; Proksch, Peter.

In: Molecular Nutrition & Food Research, Vol. 53, No. 4, 04.2009, p. 431-440.

Research output: Contribution to journalArticle

Wätjen, W, Debbab, A, Hohlfeld, A, Chovolou, Y, Kampkötter, A, Edrada, RA, Ebel, R, Hakiki, A, Mosaddak, M, Totzke, F, Kubbutat, MHG & Proksch, P 2009, 'Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation', Molecular Nutrition & Food Research, vol. 53, no. 4, pp. 431-440. https://doi.org/10.1002/mnfr.200700428
Wätjen, Wim ; Debbab, Abdessamad ; Hohlfeld, Anke ; Chovolou, Yvonni ; Kampkötter, Andreas ; Edrada, Ru Angelie ; Ebel, Rainer ; Hakiki, Abdelhak ; Mosaddak, Mahjouba ; Totzke, Frank ; Kubbutat, Michael H G ; Proksch, Peter. / Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. In: Molecular Nutrition & Food Research. 2009 ; Vol. 53, No. 4. pp. 431-440.
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abstract = "Enniatins are mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible anticancer agents. We investigated toxic effects of enniatins A1, B and B1 isolated from Fusarium tricinctum on different cancer cell lines. The enniatins showed moderate activity in HepG2 and C6 cells (EC(50)-values approximately 10-25 microM), but were highly toxic in H4IIE cells (EC(50)-values approximately 1-2.5 microM). In H4IIE cells, all enniatins increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Enniatin A1, enniatin B1, and, to a lesser extent, also enniatin B decreased the activation of extracellular regulated protein kinase (ERK) (p44/p42), a mitogen-activated protein kinase which is associated with cell proliferation. Furthermore, enniatins A1 and B1, but not enniatin B were able to inhibit moderately tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation. Screening of 24 additional protein kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) showed no inhibitory activity of enniatins. We conclude that enniatins A1 and B1 and, to a lesser extent, enniatin B may possess anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Further analysis of these substances is necessary to analyse their usefulness for cancer therapy.",
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T1 - Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation

AU - Wätjen, Wim

AU - Debbab, Abdessamad

AU - Hohlfeld, Anke

AU - Chovolou, Yvonni

AU - Kampkötter, Andreas

AU - Edrada, Ru Angelie

AU - Ebel, Rainer

AU - Hakiki, Abdelhak

AU - Mosaddak, Mahjouba

AU - Totzke, Frank

AU - Kubbutat, Michael H G

AU - Proksch, Peter

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N2 - Enniatins are mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible anticancer agents. We investigated toxic effects of enniatins A1, B and B1 isolated from Fusarium tricinctum on different cancer cell lines. The enniatins showed moderate activity in HepG2 and C6 cells (EC(50)-values approximately 10-25 microM), but were highly toxic in H4IIE cells (EC(50)-values approximately 1-2.5 microM). In H4IIE cells, all enniatins increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Enniatin A1, enniatin B1, and, to a lesser extent, also enniatin B decreased the activation of extracellular regulated protein kinase (ERK) (p44/p42), a mitogen-activated protein kinase which is associated with cell proliferation. Furthermore, enniatins A1 and B1, but not enniatin B were able to inhibit moderately tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation. Screening of 24 additional protein kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) showed no inhibitory activity of enniatins. We conclude that enniatins A1 and B1 and, to a lesser extent, enniatin B may possess anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Further analysis of these substances is necessary to analyse their usefulness for cancer therapy.

AB - Enniatins are mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible anticancer agents. We investigated toxic effects of enniatins A1, B and B1 isolated from Fusarium tricinctum on different cancer cell lines. The enniatins showed moderate activity in HepG2 and C6 cells (EC(50)-values approximately 10-25 microM), but were highly toxic in H4IIE cells (EC(50)-values approximately 1-2.5 microM). In H4IIE cells, all enniatins increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Enniatin A1, enniatin B1, and, to a lesser extent, also enniatin B decreased the activation of extracellular regulated protein kinase (ERK) (p44/p42), a mitogen-activated protein kinase which is associated with cell proliferation. Furthermore, enniatins A1 and B1, but not enniatin B were able to inhibit moderately tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation. Screening of 24 additional protein kinases involved in signal transduction pathways (cell proliferation, survival, angiogenesis and metastasis) showed no inhibitory activity of enniatins. We conclude that enniatins A1 and B1 and, to a lesser extent, enniatin B may possess anticarcinogenic properties by induction of apoptosis and disruption of ERK signalling pathway. Further analysis of these substances is necessary to analyse their usefulness for cancer therapy.

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KW - cytotoxicity

KW - enniatins

KW - ERK

KW - NF-κB

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