Rapamycin, a potent immunosuppressive drug, causes programmed cell death in B lymphoma cells.
Rapamycin, a potent immunosuppressive drug that prevents rejection of organ transplants in many animals, caused profound growth inhibition in an immature B cell lymphoma, BKS-2, at very low concentrations (2 ng/ml). Similar growth inhibition was also observed in a series of B cell lymphomas (i.e., L1.2, NFS.1.1, and WEHI-279) as well as in thymoma cells. The cell death induced by rapamycin in BKS-2 lymphoma was found to be via programmed cell death, or apoptosis. In contrast to rapamycin, neither FK506 nor CsA affected the normal growth of these cells. FK506, but not CsA antagonized the effect of rapamycin and rescued the BKS-2 cells from undergoing apoptosis. Further, suboptimal concentrations of anti-IgM antibodies and rapamycin acted synergistically in causing the growth inhibition of BKS-2 cells and this inhibitory effect was also completely reversed by FK506. Thus, rapamycin appeared to inhibit lymphoma growth by binding to FK506 binding protein. These results indicate that rapamycin should be evaluated as an effective immunosuppressive therapeutic agent to prevent the incidence of lymphoma after transplantations.
Muthukkumar
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Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0230, USA.
Ramesh
T M
TM
Bondada
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D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D011090:Polyenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D013945:Thymoma / Q000188:drug therapy; D013953:Thymus Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000888:Antibodies, Anti-Idiotypic; D007166:Immunosuppressive Agents; D011090:Polyenes; C044203:anti-IgM; D020123:Sirolimus; D016559:Tacrolimus