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.
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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)
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Chemical References |
- Antineoplastic Agents
- Cyclohexanols
- Glycoside Hydrolase Inhibitors
- cyclophellitol
- alpha-Glucosidases
- beta-Glucosidase
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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)
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