Mannosylerythritol Lipid Induced Apoptosis and Differentiation of Melanoma B16 Cells

We report here that anextracellular glycolipid, mannosylerythritol lipid (MEL), from yeast inhibited the growth of mouse melanoma B16 cells markedly in a dose-dependent manner. Exposure of B16 cells to MEL at 10 μM and higher concentrations caused the condensation of chromatin, a hallmark of cells that are undergoing apoptosis. Moreover, exposure of MEL stimulated the expression of markers of the differentiation of melanoma cells such as tyrosinase activity and the enhanced production of melanin, an indication that MEL triggered both apoptotic and cell-differentiation programs. Forced expression of Bcl-2 protein in stably transformed B 16 cells had a dual effect: it interfered with MEL-induced apoptosis but increased both tyrosinase activity and the production of melanin as compared with these phenomena in vector-transfected MEL-treated control B 16 cells. 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.