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.