Reduction of cell proliferation and potentiation of Fas-induced apoptosis by the selective kappa-opioid receptor agonist U50 488 in the multiple myeloma LP-1 cells.
As opioid receptors modulate proliferation and apoptosis of immune cells, we hypothesized that they could reduce malignant haematopoietic cells. After screening, we selected the human multiple myeloma LP-1 cells which express mu- (MOP-) and kappa-opioid receptors (KOP-R). U50 488 produces a modest but significant decrease in viability associated with an arrest in the G0/G1 phase, but not antagonized by NorBNI and not associated with modulation of p21(Cip1), p27(Kip1) or p53 expression. In contrast, no effect was observed with dynorphin, U69 593 and morphine. In conclusion, the anti-proliferative effects of U50 488 are not mediated by KOP-R in the LP-1 cells.
Kerros
Céline
C
Université de Caen, Laboratoire de biologie moléculaire et cellulaire de la signalisation, UPRES-EA 3919, IFR 146 ICORE, avenue côte de Nacre, 14032 Caen, France.
Brood
Isabelle
I
Sola
Brigitte
B
Jauzac
Philippe
P
Allouche
Stéphane
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D019014:fas Receptor / Q000819:agonists*
D018712:Analgesics, Non-Narcotic; D018797:Cell Cycle Proteins; D017473:Receptors, Opioid, kappa; D019014:fas Receptor; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer