Bryostatin 1, a unique biologic response modifier: Anti-leukemic activity in vitro

R. J. Jones, S. J. Sharkis, C. B. Miller, E. K. Rowinsky, P. J. Burke, W. S. May

Research output: Contribution to journalArticle

Abstract

Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, has demonstrated both antineoplastic activity against the murine P388 leukemia line in vivo and stimulatory activity against mouse and human hematopoietic progenitors. We studied the effects of bryostatin 1 on the growth of human leukemias in vitro. Bryostatin 1 inhibited 1 to 4 logs of clonogenic leukemia cell growth from three of four leukemia cell lines. Bryostatin 1 also inhibited, by at least 1 log, the proliferation of clonogenic acute nonlymphocytic leukemia (ANLL) cells from 10 to 12 patients with newly diagnosed or relapsed ANLL. Maximal inhibition of leukemic growth occurred at 10-9 to 10-7 mol/L bryostatin 1. Interestingly, bryostatin 1 also inhibited the growth of hematopoietic progenitors from eight patients with myelodysplastic syndromes (MDS). Leukemia cells exposed to bryostatin 1 for up to 96 hours and then washed, demonstrated no substantial inhibition of clonogenic growth, indicating that the anti-leukemic effect of bryostatin 1 is cytostatic. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) produced more potent inhibition of clonogenic leukemia growth, and this inhibition was blocked by bryostatin 1. Thus, the anti-leukemic activity of bryostatin 1 may be mediated through activation of protein kinase C. Bryostatin 1 inhibits clonogenic leukemia cells at concentrations that stimulate normal hematopoietic progenitors. The differential effects of bryostatin 1 on normal and abnormal hematopoiesis suggest that bryostatin 1 may have value in the treatment of leukemias and MDS.

Original languageEnglish (US)
Pages (from-to)1319-1323
Number of pages5
JournalBlood
Volume75
Issue number6
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jones, R. J., Sharkis, S. J., Miller, C. B., Rowinsky, E. K., Burke, P. J., & May, W. S. (1990). Bryostatin 1, a unique biologic response modifier: Anti-leukemic activity in vitro. Blood, 75(6), 1319-1323. https://doi.org/10.1182/blood.v75.6.1319.bloodjournal7561319