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, 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.
Atsumi
S
S
Institute of Microbial Chemistry, Tokyo, Japan.
Nosaka
C
C
Ochi
Y
Y
Iinuma
H
H
Umezawa
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003511:Cyclohexanols / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D000520:alpha-Glucosidases / Q000378:metabolism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D003511:Cyclohexanols; D065089:Glycoside Hydrolase Inhibitors; C063285:cyclophellitol; D000520:alpha-Glucosidases; D001617:beta-Glucosidase