Bryostatin-5 stimulates normal human hematopoiesis and inhibits proliferation of HL60 leukemic cells.
In this study we explored the effects of bryostatin-5 on the clonogenic response of normal bone marrow mononuclear (BM) cells and HL60 myeloid leukemia cells. Leukemic HL60 colony formation was strongly inhibited by bryostatin-5 depending on dose and schedule. An inhibitory effect on HL60 colony formation was readily demonstrated after 1 h of exposure, reaching a maximal inhibitory effect at 96 h. Normal BM cells differed in their clonogenic response: short-term exposure to bryostatin-5 resulted in increased clonogenicity while longstanding exposure to bryostatin-5 permitted the survival of a substantial fraction of committed progenitors. This differential modulation of normal and leukemic myeloid clonogenicity by bryostatin-5 suggests a possible role for bryostatin-5 in the treatment of acute myeloid leukemia.
Department of Hematology, Free University Hospital, Amsterdam, The Netherlands.
K G
KG
van der Hem
A M
AM
Dräger
J H
JH
Odding
M M
MM
Langenhuijsen
P C
PC
Huijgens
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D054713:Bryostatins; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D018942:Macrolides; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C078062:bryostatin 5