Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.

<h4>Background</h4>Integrins are a family of transmembrane adhesion proteins that mediate cell adhesion and intracellular signaling. Integrin-αvβ3 is expressed on the surface of human glioblastoma cells, and can be further induced by chemical stress. The Arg-Gly-Asp (RGD) motif-containin...

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Autores principales: Ming-Wei Chang, Jem-Mau Lo, Hsueh-Fen Juan, Hsin-Yi Chang, Chun-Yu Chuang
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:a5e96247eb21405582b5834a6395a8cc2021-11-18T07:17:29ZCombination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.1932-620310.1371/journal.pone.0037935https://doaj.org/article/a5e96247eb21405582b5834a6395a8cc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22655084/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Integrins are a family of transmembrane adhesion proteins that mediate cell adhesion and intracellular signaling. Integrin-αvβ3 is expressed on the surface of human glioblastoma cells, and can be further induced by chemical stress. The Arg-Gly-Asp (RGD) motif-containing peptides are specifically bound to integrin-αvβ3, and to inhibit neovasculature underlying competition to normal extracellular matrix proteins. This study employed two types of RGD peptides, cyclic RGD (c(RGDyK)) and bi-cyclic RGD (E[c(RGDyK)](2)) peptide, to human glioblastoma U87MG cells with combination of low dose Paclitaxel (PTX) pre-treatment to augment therapeutic activity for RGD peptide-induced apoptosis.<h4>Principal findings</h4>Human glioblastoma U87MG cells were treated with RGD peptides in the absence or presence of initial exposure to low-dose 10 nM PTX. Results showed that integrin-αvβ3 expressing on the surface of U87MG cells was induced by 10 nM PTX pre-treatment for 12 hrs. Additionally, the U87MG cells pre-treated with PTX and followed by RGD peptides exhibited greater expression of caspases-3, -8 and -9 than those merely treated with single agent of PTX or RGD peptide. Furthermore, the caspase-3, -8 and -9 inhibitor presented significant protection against E[c(RGDyK)](2) peptide induced U87MG programmed cell death. The increased expression of PTX-induced integrin-αvβ3 was correlated with the enhanced apoptosis in U87MG cells.<h4>Conclusions</h4>This study provides a novel concept of targeting integrin-αvβ3 with RGD peptides in combination with low-dose PTX pre-treatment to improve efficiency in human glioblastoma treatment.Ming-Wei ChangJem-Mau LoHsueh-Fen JuanHsin-Yi ChangChun-Yu ChuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37935 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ming-Wei Chang
Jem-Mau Lo
Hsueh-Fen Juan
Hsin-Yi Chang
Chun-Yu Chuang
Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
description <h4>Background</h4>Integrins are a family of transmembrane adhesion proteins that mediate cell adhesion and intracellular signaling. Integrin-αvβ3 is expressed on the surface of human glioblastoma cells, and can be further induced by chemical stress. The Arg-Gly-Asp (RGD) motif-containing peptides are specifically bound to integrin-αvβ3, and to inhibit neovasculature underlying competition to normal extracellular matrix proteins. This study employed two types of RGD peptides, cyclic RGD (c(RGDyK)) and bi-cyclic RGD (E[c(RGDyK)](2)) peptide, to human glioblastoma U87MG cells with combination of low dose Paclitaxel (PTX) pre-treatment to augment therapeutic activity for RGD peptide-induced apoptosis.<h4>Principal findings</h4>Human glioblastoma U87MG cells were treated with RGD peptides in the absence or presence of initial exposure to low-dose 10 nM PTX. Results showed that integrin-αvβ3 expressing on the surface of U87MG cells was induced by 10 nM PTX pre-treatment for 12 hrs. Additionally, the U87MG cells pre-treated with PTX and followed by RGD peptides exhibited greater expression of caspases-3, -8 and -9 than those merely treated with single agent of PTX or RGD peptide. Furthermore, the caspase-3, -8 and -9 inhibitor presented significant protection against E[c(RGDyK)](2) peptide induced U87MG programmed cell death. The increased expression of PTX-induced integrin-αvβ3 was correlated with the enhanced apoptosis in U87MG cells.<h4>Conclusions</h4>This study provides a novel concept of targeting integrin-αvβ3 with RGD peptides in combination with low-dose PTX pre-treatment to improve efficiency in human glioblastoma treatment.
format article
author Ming-Wei Chang
Jem-Mau Lo
Hsueh-Fen Juan
Hsin-Yi Chang
Chun-Yu Chuang
author_facet Ming-Wei Chang
Jem-Mau Lo
Hsueh-Fen Juan
Hsin-Yi Chang
Chun-Yu Chuang
author_sort Ming-Wei Chang
title Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
title_short Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
title_full Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
title_fullStr Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
title_full_unstemmed Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
title_sort combination of rgd compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/a5e96247eb21405582b5834a6395a8cc
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AT hsuehfenjuan combinationofrgdcompoundandlowdosepaclitaxelinducesapoptosisinhumanglioblastomacells
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