The bistratenes: new cytotoxic marine macrolides which induce some properties indicative of differentiation in HL-60 cells.
The biological effects of cytotoxic macrolide polyethers, the bistratenes, isolated from the ascidian Lissoclinum bistratum, have been examined. Bistratene A was toxic to HL-60 human promyelocytic leukemia cells with an IC50 value of 424 nM. At lower concentrations (10-100 nM), bistratene A induced the incomplete differentiation of these cells along the monocyte/macrophage pathway. These effects were not due to inhibition of DNA synthesis. Bistratene B had similar effects to bistratene A. At micromolar concentrations these compounds enhance the phospholipid-dependent activity of type II protein kinase C from bovine spleen. The bistratenes provide new probes for studying the molecular mechanisms governing cell growth and differentiation.
Watters
D
D
Department of Chemistry, University of Queensland, St Lucia, Brisbane, Australia.
Marshall
K
K
Hamilton
S
S
Michael
J
J
McArthur
M
M
Seymour
G
G
Hawkins
C
C
Gardiner
R
R
Lavin
M
M
D000081:Acetamides; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism; D011714:Pyrans; D013141:Spiro Compounds; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000081:Acetamides; D004988:Ethers, Cyclic; D010743:Phospholipids; D011714:Pyrans; D013141:Spiro Compounds; C059975:bistratene A; C059976:bistratene B; D004247:DNA; D011493:Protein Kinase C