Analysis of Differenciation Activity of Microbial Glycolipids on Animal Cells

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We found that the microbial extracellular glycolipids, succinoyl trehalose lipids (STL) induced monocytic differentiation while mannosylerythritol lipids (MEL) induced granulocytic differentiation of HL-60 human leukemia cells. In order to assess the mechanism of HL-60 cell differentiation-induction by STL, we examined the effects of analogs of STL with different hydrophobic fatty acid moieties on the growth and differentiation of HL-60 cells. Our results indicated that the effects of STL and its analogs on HL-60 cells depended on the structure of the hydrophobic moiety of STL.We also showed that MEL was a potent inhibitor of the proliferation of mouse melanoma B16 cells. Flow-cytometric analysis of the cell cycle of MEL-treated B16 cells revealed the accumulation of cells in the sub-G0/G1 phase, which is hallmark of cells undergoing apoptosis. The activity of protein kinase C (PKC) was reduced in B16 cells treated with MEL at a concentration at which induced apoptosis.Furthermore, exposure of rat pherochromocytoma PC12 cells to MEL enhanced the activity of acetylcholinesterase and interrupted the cell cycle at the G1 phase, with resulting outgrowth of neurites and partial cellular differentiation. Our results suggest that MEL induces characteristics of neuronal differentiation in PC12 cells, with transactivation of the c-jun gene, via an ERK-related signal cascade that is partially overlapping the pathways activated in response to NGF.