Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage.

KG-1a, HL-60 and U-937 cells, which represent different stages of myelopoiesis, showed growth retardation in response to the coumarin antibiotic novobiocin. Novobiocin was found to increase CD38 expression (in all three cell lines) and to induce differentiation along the monocytic path in HL-60 and U-937 cells but not in KG-1a cells. The increase in surface expression of CD38 was matched by NAD glycohydrolase activity and by increases in the level of specific mRNA, indicating that the gene product is active and that regulation occurs at the level of transcription or mRNA stability. Of the three cell lines tested, only the early KG-1a expressed N-cadherin, a member of Ca(2+)-dependent adhesion molecules involved in embryonic differentiation processes. In contrast to CD38, N-cadherin was slightly down-regulated pointing to a specific role of novobiocin in gene regulation.