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Antimitotic activity of high affinity ligands for peripheral benzodiazepine receptor (PBR) in some normal and neoplastic cell lines
- Source :
- Adv Med Sci, Adv Med Sci, 2006, 51, pp.156-9, Scopus-Elsevier, ResearcherID
- Publication Year :
- 2006
- Publisher :
- HAL CCSD, 2006.
-
Abstract
- International audience; PURPOSE: Overexpression of PBR has been found in several tumor types including ovarian, colon, breast adenocarcinomas, esophageal cancer. There is evidence suggesting that PBR ligands regulate cell proliferation. However, their action is probably cell-type specific. We decided to evaluate mitotic activity of PBR ligands in some normal and neoplastic cell lines. MATERIAL AND METHODS: The cells were maintained according to standard procedures. Ligand binding assay was performed in cell extract using PK-11195 or Ro-54864 and [N-methyl-3H] Ro-54864 or [N-methyl-3H] PK-11195. Cell proliferation was evaluated using 5-[3H]-thymidine assay. Western Immunoblot assay was conducted using polyclonal anti-PBR antibody. RESULTs: We have found that, macrophages evoked strong binding of both Ro-54864 and PK-11195. This phenomenon was accompanied by drastic decrease in the cell divisions. Similar effect was found only in the case of non-estrogen-dependent breast cancer cells MDA-MB 231. It suggest that PBR-ligand mediated inhibition of mitogenesis may represent a new anticancer strategy in non-estrogen-dependent breast cancer. In respect to macrophages inhibition of the cell division by both PBR ligands may have implication in modulation of inflammatory response. It has been postulated that PBR ligands may have anti-inflammatory activity in rheumatoid arthritis. The presence of peripheral benzodiazepine receptors in chondrocytes, T cells, macrophages and mesenchymal cells suggest that peripheral benzodiazepine receptor ligands may interfere with the cytokine network and thus modulate inflammatory response. CONCLUSIONS: The data suggest that PBR-ligand mediated inhibition of DNA synthesis in non-estrogen dependent breast cancer cells and in macrophages may represent a new therapeutic approach of breast anti-cancer and anti-inflammatory therapy.
- Subjects :
- MESH: Cell Line, Tumor
Blotting, Western
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Antimitotic Agents
Ligands
Cell Line
Cell Line, Tumor
MESH: Antimitotic Agents
MESH: Cell Proliferation
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
MESH: Isoquinolines
MESH: Ligands
Humans
MESH: Blotting, Western
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
MESH: Receptors, GABA-A
Cell Proliferation
MESH: Humans
Macrophages
MESH: Macrophages
Isoquinolines
Receptors, GABA-A
MESH: Cell Line
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Thymidine
MESH: Thymidine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Adv Med Sci, Adv Med Sci, 2006, 51, pp.156-9, Scopus-Elsevier, ResearcherID
- Accession number :
- edsair.pmid.dedup....748b5b7989945aaf3293a588264cd5d0