Mannosylerythritol lipid is a potent inducer of apoptosis and differentiation of mouse melanoma cells in culture

Malignant melanomas are tumors that are well known to respond pearly to tre atment with chemotherapeutic reagents. We report here that mannosylerythrit ol lipid (MEL), an extracellular glycolipid from yeast, markedly inhibited the growth of mouse melanoma B16 cells in a dose-dependent manner. Exposure of B16 cells to MEL at 10 pw and higher concentrations caused the condensa tion of chromatin, DNA fragmentation, and sub-G(1) arrest, all of which are hallmarks of cells that are undergoing apoptosis. Analysis of the cell cyc le also suggested that both the MEL-mediated inhibition of growth and apopt osis were closely associated with growth arrest in the G(1) phase. Moreover , MEL exposure stimulated the expression of differentiation markers of mela noma cells, such as tyrosinase activity and the enhanced production of mela nin, which is an indication that MEL triggered both apoptotic and cell diff erentiation programs, Forced expression of Bcl-2 protein in stably transfor med B16 cells had a dual effect: it interfered with MEL-induced apoptosis b ut increased both tyrosinase activity and the production of melanin as comp ared dth these phenomena in vector-transfected NEL-treated control B16 cell s. These results provide the first evidence that growth arrest, apoptosis, and the differentiation of mouse malignant melanoma cells can be induced by a microbial extracellular glycolipid.