Stimulation of cell growth and DNA synthesis by peripheral benzodiazepine.
The effects of peripheral benzodiazepine receptor ligands on cell proliferation were evaluated. PK11195 increased the growth rate of C6 glioma cells by 20-30% in the nanomolar range in serum free medium. [3H]thymidine incorporation into C6 glioma cells also were increased 22% and 25% after treatment by PK11195 and Ro5-4864, respectively. The effect of PK11195 as a mitogenic agent was estimated by mitogenic agent was estimated by [3H]thymidine incorporation using Swiss 3T3 cells. PK11195 increased DNA synthesis 170% over control at 10 nM. Higher concentrations of benzodiazepines showed inhibition of the DNA synthesis. Peripheral benzodiazepine binding sites underwent downregulation after exposure to serum free medium or to 10 nM PK11195. These findings suggest that peripheral benzodiazepines may be involved in the regulation of cell proliferation as a growth factor in lower concentration and as a antiproliferative agent in higher concentration.
Ikezaki
K
K
Jonsson Cancer Center, Division of Neurosurgery, UCLA School of Medicine 90024.
Black
K L
KL
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001570:Benzodiazepinones; D004273:DNA, Neoplasm; D007546:Isoquinolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D013936:Thymidine; C037850:PK 11195