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 m ushroom, Volvariella volvacea, was studied using a battery of cultured tumo r cell lines. It was revealed that [H-3]thymidine incorporation into the ce ll lines was markedly reduced at 0.32 muM VVL. When S180 mouse sarcoma cell s were incubated for 48 hr with doses of VVL ranging from 0.32 to 0.8 muM, prominent blebs on the cell surface and large vacuoles in the cytoplasm, bu t not apoptotic bodies, were observed under a fluorescence microscopy. VVL did not exert ribosome-inactivating activity or induce any changes in the e xpression 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-depend ent 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. (C) 2000 Elsevier Science Inc. All rights reserved.