Co-induction of lymphokine synthesis by the antineoplastic bryostatins.
The macrocyclic lactone bryostatins, isolated from marine bryozoans, have been found to be strong inhibitors of e.g., the P 388 murine lymphocyte leukemia cell line and in vivo systems. Presently, bryostatin 1 is under preclinical development as a potential anticancer drug, although the bryostatins exhibit some of the same biological effects as the tumor promoting phorbol-12-myristate-13-acetate (PMA), especially activation of protein kinase C in certain cell types. In our experiments, we investigated the influence of bryostatin 1 on the synthesis of interleukin 2 (IL2) and interferon-gamma (IFN-gamma) by ionophore A23187 or mitogen-induced human blood lymphocytes. These results were then compared with those achieved using the two tumor promotors PMA and teleocidin. Our data indicate that bryostatin 1 is comparable to these two other drugs in increasing production of the two lymphokines 10-100-fold. The IL2 and IFN-gamma production kinetics of cultures induced with either A23187/bryostatin 1 or A23187/PMA were practically identical. The general pattern of peptides, however, released from bryostatin 1 coinduced cultures differed from that obtained when PMA was used.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis*; D018942:Macrolides; D008934:Mitogens / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000970:Antineoplastic Agents; D054713:Bryostatins; D007376:Interleukin-2; D007783:Lactones; D008222:Lymphokines; D018942:Macrolides; D008934:Mitogens; D000001:Calcimycin; C046785:bryostatin 1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate