Inhibition of experimental metastasis by an alpha-glucosidase inhibitor, 1,6-epi-cyclophellitol.

Abstract

Isolated from a culture filtrate of Phellinus sp., cyclophellitol is a specific inhibitor of beta-glucosidase, but unlike castanospermine, it does not inhibit experimental metastasis. However, its structural analogue, 1,6-epi-cyclophellitol, inhibited alpha-glucosidase as well as beta-glucosidase, and inhibited experimental metastasis. 1,6-Epi-cyclophellitol depressed alpha-glucosidase activity in cultured B16/F10 cells after 48 h of incubation. Preincubation of B16/F10 cells for 48 h with 1,6-epi-cyclophellitol inhibited invasion of the cells in a Boyden chamber assay at the doses effective in inhibiting alpha-glucosidase in situ. Pulmonary metastasis of B16/F10 cells in mice was inhibited by pretreatment of the cells with 1,6-epi-cyclophellitol in culture. The inhibitor reduced the collagen type I- and IV-mediated attachment of the cells, whereas it had no effect on laminin-mediated attachment. These results suggest that alpha-glucosidase in tumor cells is essential for the metastatic process through the cellular interaction with collagen type I and IV.

• Authors: S Atsumi, C Nosaka, Y Ochi, H Iinuma, K Umezawa
• Journal: Cancer research (Cancer Res) Vol. 53 Issue 20 Pg. 4896-9 (Oct 15 1993) ISSN: 0008-5472 [Print] United States
• PMID: 8402678 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cyclohexanols
• Glycoside Hydrolase Inhibitors
• cyclophellitol
• alpha-Glucosidases
• beta-Glucosidase

Topics

• Animals
• Antineoplastic Agents (therapeutic use, toxicity)
• Cell Adhesion (drug effects)
• Cell Line
• Cyclohexanols (therapeutic use, toxicity)
• Female
• Glycoside Hydrolase Inhibitors
• Kinetics
• Lung Neoplasms (pathology, prevention & control, secondary)
• Melanoma, Experimental (drug therapy, enzymology, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Invasiveness
• Neoplasm Metastasis (prevention & control)
• alpha-Glucosidases (metabolism)
• beta-Glucosidase (antagonists & inhibitors, metabolism)