Growth modulation and differentiation of acute myeloid leukemia cells by jaspamide.
We have examined the effect of Jaspamide, a peptide isolated from the marine sponge Hemiastrella minor, on in vitro proliferation and differentiation of leukemic cell lines and blast cells of three AML patients and compared it to that of cytosine arabinoside (ARA-C). The biological properties were studied in two complementary culture methods. The first is a clonogenic assay that supports colony formation in agar and reflects terminal divisions. The second is a suspension assay in which clonogenic cells increase exponentially and which reflects self-renewal. Jaspamide, at micromolar concentrations and in a dose-dependent manner, suppressed both primary colony formation in agar and the recovery of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, Jaspamide was more effective in inhibiting clonogenic cells grown in suspension than primary colonies grown in agar. In addition, Jaspamide, similarly to ARA-C, was able to induce immunophenotypic maturation of leukemic cell lines (upregulation of CD14 and CD11 and downregulation of CD34 antigens). Our results indicate that Jaspamide significantly inhibits the self-renewal capacity of leukemic progenitors and may provide a new useful tool for the treatment of acute myeloid leukemia (AML) patients.
Fabian
I
I
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
Shur
I
I
Bleiberg
I
I
Rudi
A
A
Kashman
Y
Y
Lishner
M
M
D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D047630:Depsipeptides; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D047630:Depsipeptides; D010456:Peptides, Cyclic; D003561:Cytarabine; C057531:jasplakinolide