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Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human esophageal cancer cells
Author(s) -
Sutter Andreas P.,
Maaser Kerstin,
Höpfner Michael,
Barthel Bettina,
Grabowski Patricia,
Faiss Siegbert,
Carayon Pierre,
Zeitz Martin,
Scherübl Hans
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10724
Subject(s) - apoptosis , cell cycle , cell cycle checkpoint , cell growth , cancer research , cell , esophageal cancer , dna fragmentation , fragmentation (computing) , biology , cancer cell , cell culture , receptor , programmed cell death , cancer , chemistry , microbiology and biotechnology , biochemistry , genetics , ecology
Esophageal cancer is the most markedly increasing tumor entity in Western countries. Due to very poor 5‐year‐survival, new therapeutic approaches are mandatory. Peripheral benzodiazepine receptors (PBR) have been implicated in growth control of various tumor models, but they have not been studied yet in esophageal cancer. We used esophageal cancer cell lines and primary cell cultures of human esophageal cancers and evaluated (i) expression and localization of PBR; (ii) PBR‐ligand‐induced inhibition of cell growth; (iii) induction of apoptosis; and (iv) alterations in cell cycle. Expression of PBR was detected both in cell lines and in primary cell cultures of human esophageal cancers. PBR was localized in the mitochondria. The PBR‐specific ligands FGIN‐1‐27 and PK 11195, but not the centrally acting benzodiazepine clonazepam or the indolacetamide FGIN‐1‐52, neither of which displaying any affinity to the PBR, inhibited cell proliferation. FGIN‐1‐27 and PK 11195, but not clonazepam, potently induced apoptosis. FGIN‐1‐27 was shown to sequentially decrease the mitochondrial membrane potential, then to activate caspase‐3 and finally to cause DNA fragmentation. In addition, PBR‐specific ligands induced cell cycle arrest in the G1/G0 phase. Our data qualify PBR‐specific ligands as innovative proapoptotic and antiproliferative substances. They might prove suitable for the treatment of esophageal cancer. © 2002 Wiley‐Liss, Inc.