BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Amanda Thomaz; Mariane Jaeger; Marienela Buendia; Victorio Bambini-Junior; Lauro José Gregianin; Algemir Lunardi Brunetto; André T Brunetto; Caroline Brunetto de Farias; Rafael Roesler

doi:10.1007/s12031-015-0689-0

BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Amanda Thomaz
, Mariane Jaeger
, Marienela Buendia
, Victorio Bambini-Junior
, Lauro José Gregianin
, Algemir Lunardi Brunetto
, André T Brunetto
, Caroline Brunetto de Farias
, Rafael Roesler

Biology

Universidade Federal do Rio Grande do Sul
Laboratory of Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 21040-360, Rio de Janeiro, RJ, Brazil

Research output: Contribution to journal › Article (journal) › peer-review

16 Citations (Scopus)

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

Original language	English
Pages (from-to)	326-333
Number of pages	8
Journal	Journal of Molecular Neuroscience
Volume	59
Issue number	3
DOIs	https://doi.org/10.1007/s12031-015-0689-0
Publication status	Published - 27 Nov 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antineoplastic Agents/pharmacology
Azepines/pharmacology
Benzamides/pharmacology
Brain Neoplasms/metabolism
Brain-Derived Neurotrophic Factor/pharmacology
Cell Line, Tumor
Cell Proliferation/drug effects
Cell Survival/drug effects
Humans
Medulloblastoma/metabolism
Membrane Glycoproteins/antagonists & inhibitors
Protein Kinase Inhibitors/pharmacology
Protein-Tyrosine Kinases/antagonists & inhibitors
Receptor, trkB
Signal Transduction

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10.1007/s12031-015-0689-0

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Thomaz, A., Jaeger, M., Buendia, M., Bambini-Junior, V., Gregianin, L. J., Brunetto, A. L., Brunetto, A. T., de Farias, C. B., & Roesler, R. (2015). BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells. Journal of Molecular Neuroscience, 59(3), 326-333. https://doi.org/10.1007/s12031-015-0689-0

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title = "BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells",

abstract = "Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.",

keywords = "Antineoplastic Agents/pharmacology, Azepines/pharmacology, Benzamides/pharmacology, Brain Neoplasms/metabolism, Brain-Derived Neurotrophic Factor/pharmacology, Cell Line, Tumor, Cell Proliferation/drug effects, Cell Survival/drug effects, Humans, Medulloblastoma/metabolism, Membrane Glycoproteins/antagonists \& inhibitors, Protein Kinase Inhibitors/pharmacology, Protein-Tyrosine Kinases/antagonists \& inhibitors, Receptor, trkB, Signal Transduction",

author = "Amanda Thomaz and Mariane Jaeger and Marienela Buendia and Victorio Bambini-Junior and Gregianin, \{Lauro Jos{\'e}\} and Brunetto, \{Algemir Lunardi\} and Brunetto, \{Andr{\'e} T\} and \{de Farias\}, \{Caroline Brunetto\} and Rafael Roesler",

year = "2015",

month = nov,

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doi = "10.1007/s12031-015-0689-0",

language = "English",

volume = "59",

pages = "326--333",

journal = "Journal of Molecular Neuroscience",

issn = "0895-8696",

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Thomaz, A, Jaeger, M, Buendia, M, Bambini-Junior, V, Gregianin, LJ, Brunetto, AL, Brunetto, AT, de Farias, CB & Roesler, R 2015, 'BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells', Journal of Molecular Neuroscience, vol. 59, no. 3, pp. 326-333. https://doi.org/10.1007/s12031-015-0689-0

TY - JOUR

T1 - BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors

T2 - Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

AU - Thomaz, Amanda

AU - Jaeger, Mariane

AU - Buendia, Marienela

AU - Bambini-Junior, Victorio

AU - Gregianin, Lauro José

AU - Brunetto, Algemir Lunardi

AU - Brunetto, André T

AU - de Farias, Caroline Brunetto

AU - Roesler, Rafael

PY - 2015/11/27

Y1 - 2015/11/27

N2 - Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

AB - Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

KW - Antineoplastic Agents/pharmacology

KW - Azepines/pharmacology

KW - Benzamides/pharmacology

KW - Brain Neoplasms/metabolism

KW - Brain-Derived Neurotrophic Factor/pharmacology

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Cell Survival/drug effects

KW - Humans

KW - Medulloblastoma/metabolism

KW - Membrane Glycoproteins/antagonists & inhibitors

KW - Protein Kinase Inhibitors/pharmacology

KW - Protein-Tyrosine Kinases/antagonists & inhibitors

KW - Receptor, trkB

KW - Signal Transduction

U2 - 10.1007/s12031-015-0689-0

DO - 10.1007/s12031-015-0689-0

M3 - Article (journal)

SN - 0895-8696

VL - 59

SP - 326

EP - 333

JO - Journal of Molecular Neuroscience

JF - Journal of Molecular Neuroscience

IS - 3

ER -

BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Abstract

UN SDGs

Keywords

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