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Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS

Standard

Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS. / Reuss, David E; Mucha, Jana; Hagenlocher, Christian; Ehemann, Volker; Kluwe, Lan; Mautner, Victor-Felix; von Deimling, Andreas.

In: PLOS ONE, Vol. 8, No. 2, 01.01.2013, p. e57152.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Reuss, DE, Mucha, J, Hagenlocher, C, Ehemann, V, Kluwe, L, Mautner, V-F & von Deimling, A 2013, 'Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS', PLOS ONE, vol. 8, no. 2, pp. e57152. https://doi.org/10.1371/journal.pone.0057152

APA

Reuss, D. E., Mucha, J., Hagenlocher, C., Ehemann, V., Kluwe, L., Mautner, V-F., & von Deimling, A. (2013). Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS. PLOS ONE, 8(2), e57152. https://doi.org/10.1371/journal.pone.0057152

Vancouver

Reuss DE, Mucha J, Hagenlocher C, Ehemann V, Kluwe L, Mautner V-F et al. Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS. PLOS ONE. 2013 Jan 1;8(2):e57152. https://doi.org/10.1371/journal.pone.0057152

Bibtex

@article{31816646ec204b1ba6a7b2347a910d39,
title = "Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS",
abstract = "Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS.",
keywords = "Acetylcysteine, Antineoplastic Agents, Phytogenic, Apoptosis, Cell Cycle Proteins, Cell Line, Tumor, Curcumin, Gene Expression Regulation, Neoplastic, Humans, MAP Kinase Signaling System, Nerve Sheath Neoplasms, Neurofibromatosis 1, Neurofibromin 1, Nuclear Proteins, Phosphatidylinositol 3-Kinases, Protein Structure, Tertiary, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-myc, Reactive Oxygen Species, Receptors, TNF-Related Apoptosis-Inducing Ligand, Schwann Cells, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand",
author = "Reuss, {David E} and Jana Mucha and Christian Hagenlocher and Volker Ehemann and Lan Kluwe and Victor-Felix Mautner and {von Deimling}, Andreas",
year = "2013",
month = jan,
day = "1",
doi = "10.1371/journal.pone.0057152",
language = "English",
volume = "8",
pages = "e57152",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS

AU - Reuss, David E

AU - Mucha, Jana

AU - Hagenlocher, Christian

AU - Ehemann, Volker

AU - Kluwe, Lan

AU - Mautner, Victor-Felix

AU - von Deimling, Andreas

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS.

AB - Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS.

KW - Acetylcysteine

KW - Antineoplastic Agents, Phytogenic

KW - Apoptosis

KW - Cell Cycle Proteins

KW - Cell Line, Tumor

KW - Curcumin

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - MAP Kinase Signaling System

KW - Nerve Sheath Neoplasms

KW - Neurofibromatosis 1

KW - Neurofibromin 1

KW - Nuclear Proteins

KW - Phosphatidylinositol 3-Kinases

KW - Protein Structure, Tertiary

KW - Proto-Oncogene Proteins c-akt

KW - Proto-Oncogene Proteins c-myc

KW - Reactive Oxygen Species

KW - Receptors, TNF-Related Apoptosis-Inducing Ligand

KW - Schwann Cells

KW - Signal Transduction

KW - TNF-Related Apoptosis-Inducing Ligand

U2 - 10.1371/journal.pone.0057152

DO - 10.1371/journal.pone.0057152

M3 - SCORING: Journal article

C2 - 23437333

VL - 8

SP - e57152

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 2

ER -