Suppression of cell cycle progression by a fungal lectin: activation of cyclin-dependent kinase inhibitors.
The antiproliferative activity of a fungal lectin (VVL) isolated from the mushroom, Volvariella volvacea, was studied using a battery of cultured tumor cell lines. It was revealed that [(3)H]thymidine incorporation into the cell lines was markedly reduced at 0.32 microM VVL. When S180 mouse sarcoma cells were incubated for 48 hr with doses of VVL ranging from 0.32 to 0.8 microM, prominent blebs on the cell surface and large vacuoles in the cytoplasm, but not apoptotic bodies, were observed under a fluorescence microscopy. VVL did not exert ribosome-inactivating activity or induce any changes in the expression of cyclins A, D1, and E. However, it did activate the expression of cyclin kinase inhibitors, namely p21, p27, p53, and Rb, in a dose-dependent manner. Flow cytometric analysis demonstrated an accumulation of cells in the G2/M phase in a time- and dose-dependent manner, indicating that VVL arrested cell proliferation by blocking cell cycle progression in the G2/M phase.
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Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. ken-liu@cuhk.edu.hk
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D000363:Agaricales / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D005656:Fungal Proteins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D051379:Mice; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism; D012276:Ricin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016213:Cyclins; D005656:Fungal Proteins; D037102:Lectins; D012276:Ricin