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Co-induction of lymphokine synthesis by the antineoplastic bryostatins.

Abstract
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.
AuthorsH Mohr, G R Pettit, A Plessing-Menze
JournalImmunobiology (Immunobiology) Vol. 175 Issue 5 Pg. 420-30 (Nov 1987) ISSN: 0171-2985 [Print] Netherlands
PMID3123367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Bryostatins
  • Interleukin-2
  • Lactones
  • Lymphokines
  • Macrolides
  • Mitogens
  • Calcimycin
  • bryostatin 1
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate
Topics
  • Antineoplastic Agents (pharmacology)
  • Bryostatins
  • Calcimycin (pharmacology)
  • Humans
  • In Vitro Techniques
  • Interferon-gamma (biosynthesis)
  • Interleukin-2 (biosynthesis)
  • Kinetics
  • Lactones (pharmacology)
  • Lymphocytes (drug effects, immunology)
  • Lymphokines (biosynthesis)
  • Macrolides
  • Mitogens (pharmacology)
  • Tetradecanoylphorbol Acetate (pharmacology)

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