INHIBITION OF EXPERIMENTAL METASTASIS BY AN ALPHA-GLUCOSIDASE INHIBITOR, 1,6-EPI-CYCLOPHELLITOL

Isolated from a culture filtrate of Phellinus sp., cyclophellitol is a specific inhibitor of beta-glucosidase, but unlike castanospermine, i t does not inhibit experimental metastasis. However, its structural an alogue, 1,6-epicyclophellitol, inhibited alpha-glucosidase as well as beta-glucosidase, and inhibited experimental metastasis. 1,6-Epi-cyclo phellitol depressed alpha-glucosidase activity in cultured B16/F10 cel ls after 48 h of incubation. Preincubation of B16/F10 cells for 48 h w ith 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 b y pretreatment of the cells with 1,6-epicyclophellitol 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. Th ese results suggest that alpha-glucosidase in tumor cells is essential for the metastatic process through the cellular interaction with coll agen type I and IV.