Antitumor Activities and Cellular Changes Induced by TrkB Inhibition in Medulloblastoma

Bibliographic Details
Title: Antitumor Activities and Cellular Changes Induced by TrkB Inhibition in Medulloblastoma
Authors: Amanda Thomaz, Kelly de Vargas Pinheiro, Bárbara Kunzler Souza, Lauro Gregianin, Algemir L. Brunetto, André T. Brunetto, Caroline Brunetto de Farias, Mariane da Cunha Jaeger, Vijay Ramaswamy, Carolina Nör, Michael D. Taylor, Rafael Roesler
Source: Frontiers in Pharmacology, Vol 10 (2019)
Publisher Information: Frontiers Media S.A., 2019.
Publication Year: 2019
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: brain-derived neurotrophic factor, tropomyosin receptor kinase B, neurotrophin, medulloblastoma, brain tumor, Therapeutics. Pharmacology, RM1-950
More Details: Neurotrophins are critically involved in regulating normal neural development and plasticity. Brain-derived neurotrophic factor (BDNF), a neurotrophin that acts by binding to the tropomyosin receptor kinase B (TrkB) receptor, has also been implicated in the progression of several types of cancer. However, its role in medulloblastoma (MB), the most common type of malignant brain tumor afflicting children, remains unclear. Here we show that selective TrkB inhibition with the small molecule compound ANA-12 impaired proliferation and viability of human UW228 and D283 MB cells, and slowed the growth of MB tumors xenografted into nude mice. These effects were accompanied by increased apoptosis, reduced extracellular-regulated kinase (ERK) activity, increased expression of signal transducer and activator of transcription 3 (STAT3), and differential modulation of p21 expression dependent on the cell line. In addition, MB cells treated with ANA-12 showed morphological alterations consistent with differentiation, increased levels of the neural differentiation marker β-III Tubulin (TUBB3), and reduced expression of the stemness marker Nestin. These findings are consistent with the possibility that selective TrkB inhibition can display consistent anticancer effects in MB, possibly by modulating intracellular signaling and gene expression related to tumor progression, apoptosis, and differentiation.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1663-9812
Relation: https://www.frontiersin.org/article/10.3389/fphar.2019.00698/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2019.00698
Access URL: https://doaj.org/article/b5b0e0b16162448d9954f355f8f89f01
Accession Number: edsdoj.b5b0e0b16162448d9954f355f8f89f01
Database: Directory of Open Access Journals
More Details
ISSN:16639812
DOI:10.3389/fphar.2019.00698
Published in:Frontiers in Pharmacology
Language:English