Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines : a mechanism for induction of apoptosis via the 18 kDa mitochondrial translocator protein.

Apoptosis : an International Journal on Programmed Cell Death
Leo VeenmanWilfried Kugler

Abstract

Erucylphosphohomocholine (ErPC3, Erufosine) was reported previously to induce apoptosis in otherwise highly apoptosis-resistant malignant glioma cell lines while sparing their non-tumorigenic counterparts. We also previously found that the mitochondrial 18 kDa Translocator Protein (TSPO) is required for apoptosis induction by ErPC3. These previous studies also suggested involvement of reactive oxygen species (ROS). In the present study we further investigated the potential involvement of ROS generation, the participation of the mitochondrial respiration chain, and the role of the mitochondrial F(O)F(1)-ATP(synth)ase in the pro-apoptotic effects of ErPC3 on U87MG and U118MG human glioblastoma cell lines. For this purpose, cells were treated with the ROS chelator butylated hydroxyanisole (BHA), the mitochondrial respiration chain inhibitors rotenone, antimycin A, myxothiazol, and the uncoupler CCCP. Also oligomycin and piceatannol were studied as inhibitors of the F(O) and F(1) subunits of the mitochondrial F(O)F(1)-ATP(synth)ase, respectively. BHA was able to attenuate apoptosis induction by ErPC3, including mitochondrial ROS generation as determined with cardiolipin oxidation, as well as collapse of the mitochondrial membrane p...Continue Reading

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Citations

Apr 29, 2011·Cancer Chemotherapy and Pharmacology·Rebecca G BagleyBeverly A Teicher
May 1, 2012·Apoptosis : an International Journal on Programmed Cell Death·Luba ShargorodskyMoshe Gavish
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Jul 3, 2021·Frontiers in Molecular Biosciences·Sharad Kumar SutharSang-Yoon Lee

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Methods Mentioned

BETA
ELISA
protein assay
fluorescence assisted cell sorting
flow cytometry
FACS
Assay

Software Mentioned

CellQuest
GraphPad

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