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

Ming Wei Chang, Jem Mau Lo, Hsueh Fen Juan, Hsin Yi Chang, Chun Yu Chuang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: 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. Principal Findings: 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. Conclusions: 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.

Original languageEnglish
Article numbere37935
JournalPLoS One
Volume7
Issue number5
DOIs
Publication statusPublished - May 24 2012
Externally publishedYes

Fingerprint

paclitaxel
Glioblastoma
Paclitaxel
Integrins
integrins
apoptosis
peptides
Apoptosis
dosage
cells
Caspase 8
pretreatment
Caspase 3
caspase-3
Peptides
cyclic peptides
Extracellular Matrix Proteins
Cell adhesion
Cell death
Cell Adhesion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells. / Chang, Ming Wei; Lo, Jem Mau; Juan, Hsueh Fen; Chang, Hsin Yi; Chuang, Chun Yu.

In: PLoS One, Vol. 7, No. 5, e37935, 24.05.2012.

Research output: Contribution to journalArticle

Chang, Ming Wei ; Lo, Jem Mau ; Juan, Hsueh Fen ; Chang, Hsin Yi ; Chuang, Chun Yu. / Combination of RGD compound and low-dose paclitaxel induces apoptosis in human glioblastoma cells. In: PLoS One. 2012 ; Vol. 7, No. 5.
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