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PIGA ( N , N ‐Di‐ n ‐butyl‐5‐chloro‐2‐(4‐chlorophenyl)indol‐3‐ylglyoxylamide), a New Mitochondrial Benzodiazepine‐Receptor Ligand, Induces Apoptosis in C6 glioma Cells
Author(s) -
Chelli Beatrice,
Rossi Leonardo,
Da Pozzo Eleonora,
Costa Barbara,
Spinetti Francesca,
Rechichi Mariarosa,
Salvetti Alessandra,
Lena Annalisa,
Simorini Francesca,
Vanacore Renato,
Scatena Fabrizio,
Da Settimo Federico,
Gremigni Vittorio,
Martini Claudia
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400350
Subject(s) - apoptosis , cytochrome c , biology , dna fragmentation , mitochondrion , glioma , programmed cell death , ligand (biochemistry) , microbiology and biotechnology , carcinogenesis , membrane potential , receptor , cancer research , chemistry , biochemistry , gene
Mitochondrial benzodiazepine‐receptor (mBzR) ligands constitute a heterogeneous class of compounds that show a pleiotropic spectrum of effects within the cells, including the modulation of apoptosis. In this paper, a novel synthetic 2‐phenylindol‐3‐ylglyoxylamide derivative, N,N ‐di‐ n ‐butyl‐5‐chloro‐2‐(4‐chlorophenyl)indol‐3‐ylglyoxylamide (PIGA), which shows high affinity and selectivity for the mBzR, is demonstrated to induce apoptosis in rat C6 glioma cells. PIGA was able to dissipate mitochondrial transmembrane potential (Δ Ψ m) and to cause a significant cytosolic accumulation of cytochrome c. Moreover, typical features of apoptotic cell death, such as caspase‐3 activation and DNA fragmentation, were also detected in PIGA‐treated cells. Our data expand the knowledge on mBzR ligand‐mediated apoptosis and suggest PIGA as a novel proapoptotic compound with therapeutic potential against glial tumours, in which apoptosis resistance has been reported to be involved in carcinogenesis.