Macrosphelide B suppressed metastasis through inhibition of adhesion of sLe(x)/E-selectin molecules.

Abstract

Macrosphelide B (MSB), a 16-membered macrolide from Microsphaeropsis sp. FO-5050, inhibits adhesion of sialyl Lewis(x) (sLe(x))-expressing HL-60 cells to LPS-activated (E-selectin-expressing) human umbilical vein endothelial cells (HUVECs) in vitro. This study examines MSB effects on metastasis of B16/BL6 mouse melanoma cells (B16/BL6 cells) and L5178Y-ML mouse lymphoma cells in vivo and analyzes the MSB antimetastatic activity mechanism. When administered MSB at 20 mg/kg/day, lung metastatic nodules of B16/BL6 cells were significantly decreased (T/C = 45%). However, no inhibition of metastasis of L5178Y-ML cells to the spleen and liver was observed. Flow cytometry analysis showed that B16/BL6 cells expressed high levels of sLe(x) antigen, whereas expression on L5178Y-ML cells was low. Under in vitro conditions, B16/BL6 cells demonstrated a greater degree of adhesion to LPS-activated HUVECs than L5178Y-ML cells, but adhesion was significantly inhibited by MSB and sLe(x) antibody. Combined therapy of MSB and cisplatin (CDDP) induced remarkable lung metastasis inhibition without adverse effects of CDDP to the host. All these findings suggest that MSB suppresses lung metastasis of B16/BL6 cells by inhibiting cell adhesion to endothelial cells through the sLe(x) molecule.

• Authors: Akiko Fukami, Kousuke Iijima, Masahiko Hayashi, Kanki Komiyama, Satoshi Omura
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 291 Issue 4 Pg. 1065-70 (Mar 08 2002) ISSN: 0006-291X [Print] United States
• PMID: 11866473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cell Adhesion Molecules
• E-Selectin
• Heterocyclic Compounds
• Oligosaccharides
• Sialyl Lewis X Antigen
• macrosphelide B
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Adhesion (drug effects)
• Cell Adhesion Molecules (metabolism)
• Cell Division (drug effects)
• Cells, Cultured
• Cisplatin (therapeutic use)
• Dose-Response Relationship, Drug
• E-Selectin (metabolism)
• Endothelium, Vascular (physiology)
• HL-60 Cells
• Heterocyclic Compounds (chemistry, pharmacology, therapeutic use)
• Humans
• Lymphoma (metabolism, pathology)
• Melanoma, Experimental (metabolism, pathology)
• Mice
• Neoplasm Metastasis (prevention & control)
• Oligosaccharides (metabolism)
• Sialyl Lewis X Antigen