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Effect of bexarotene on differentiation of glioblastoma multiforme compared with ATRA

Title
Effect of bexarotene on differentiation of glioblastoma multiforme compared with ATRA
Authors
Heo, JC[Heo, Jin-Chul]Jung, TH[Jung, Tae-Hoon]Lee, S[Lee, Sungjin]Kim, HY[Kim, Hyun Young]Choi, G[Choi, Gildon]Jung, M[Jung, Myungeun]Jung, D[Jung, Daeyoung]Lee, HK[Lee, Heung Kyoung]Lee, JO[Lee, Jung-Ok]Park, JH[Park, Ji-Hwan]Hwang, D[Hwang, Daehee]Seol, HJ[Seol, Ho Jun]Cho, H[Cho, Heeyeong]
DGIST Authors
Hwang, D[Hwang, Daehee]
Issue Date
2016-06
Citation
Clinical and Experimental Metastasis, 33(5), 417-429
Type
Article
Article Type
Article
ISSN
0262-0898
Abstract
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Since differentiation can attenuate or halt the growth of tumor cells, an image-based phenotypic screening was performed to find out drugs inducing morphological differentiation of GBMs. Bexarotene, a selective retinoid X receptor agonist, showed strong inhibition of neurospheroidal colony formation and migration of cultured primary GBM cells. Bexarotene treatment reduced nestin expression, while significantly increasing glial fibrillary acidic protein (GFAP) expression. The effect of bexarotene on gene expression profile was compared with the activity of all-trans retinoic acid (ATRA), a well-known differentiation inducer. Both drugs largely altered the gene expression pattern into a tumor-ameliorating direction. These drugs increased the gene expression levels of Kruppel-like factor 9 (KLF9), regulator of G-protein signaling 4 (RGS4), growth differentiation factor 15 (GDF15), angiopoietin-like protein 4 (ANGPTL4), and lowered the level of chemokine receptor type 4 (CXCR4). However, transglutaminase 2 (TG2) induction, an adverse effect of ATRA, was much weaker in bexarotene treated primary GBM cells. Consistently, the TG2 enzymatic activity was negligibly affected by bexarotene treatment. It is important to control TG2 overexpression since its upregulation is correlated with tumor transformation and drug resistance. Bexarotene also showed in vivo tumoricidal effects in a GBM xenograft mouse model. Therefore, we suggest bexarotene as a more beneficial differentiation agent than ATRA for GBM.
URI
http://hdl.handle.net/20.500.11750/2682
DOI
10.1007/s10585-016-9786-x
Publisher
Springer
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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