The role of growth factors in the activity of pharmacological differentiation agents.

TitleThe role of growth factors in the activity of pharmacological differentiation agents.
Publication TypeJournal Article
Year of Publication2002
AuthorsMatsui WH, Gladstone DE, Vala MS, Barber JP, Brodsky RA, Smith DB, Jones RJ
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume13
Issue6
Pagination275-83
Date Published2002 Jun
Abstract

Bryostatin-1 inhibits acute myeloid leukemia (AML) in vitroat doses that stimulate the growth of normal hematopoietic progenitors.Although bryostatin-1 has a number of distinct biological activities, those specifically responsible for its antileukemic activity are unclear. We found that bryostatin-1 (10(-8) M) inhibited cell cycling at G(1), induced phenotypic evidence of differentiation, and limited the clonogenic growth of both AML cell lines and patient specimens. This activity was markedly enhanced by granulocyte/macrophage-colony stimulating factor, whereas growth factor-neutralizing antibodies completely inhibited both the differentiating and antileukemic activities of bryostatin-1. Cell cycle inhibition and growth factors were also required for the differentiating activities of two unrelated agents, hydroxyurea and phenylbutyrate. These data suggest that many pharmacological differentiating agents require both cell cycle arrest and lineage-specific growth factors for full activity and may explain why these agents have demonstrated only limited clinical efficacy.

Alternate JournalCell Growth Differ.