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

Abstract
Malignant melanomas are tumors that are well known to respond poorly to treatment with chemotherapeutic reagents. We report here that mannosylerythritol 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 microM and higher concentrations caused the condensation of chromatin, DNA fragmentation, and sub-G1 arrest, all of which are hallmarks of cells that are undergoing apoptosis. Analysis of the cell cycle also suggested that both the MEL-mediated inhibition of growth and apoptosis were closely associated with growth arrest in the G1 phase. Moreover, MEL exposure stimulated the expression of differentiation markers of melanoma cells, such as tyrosinase activity and the enhanced production of melanin, which is an indication that MEL triggered both apoptotic and cell differentiation programs. Forced expression of Bcl-2 protein in stably transformed B16 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 B16 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.
AuthorsX Zhao, Y Wakamatsu, M Shibahara, N Nomura, C Geltinger, T Nakahara, T Murata, K K Yokoyama
JournalCancer research (Cancer Res) Vol. 59 Issue 2 Pg. 482-6 (Jan 15 1999) ISSN: 0008-5472 [Print] United States
PMID9927066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycolipids
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Kinase C
Topics
  • Animals
  • Apoptosis (drug effects)
  • Candida (chemistry)
  • Cell Cycle (drug effects)
  • Cell Differentiation (drug effects)
  • Dose-Response Relationship, Drug
  • Glycolipids (pharmacology)
  • Melanoma, Experimental (pathology)
  • Mice
  • Protein Kinase C (physiology)
  • Proto-Oncogene Proteins c-bcl-2 (analysis)

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