INVITRO EFFECT OF FUNGAL CYCLODEPSIPEPTIDES ON LEUKEMIC-CELLS - STUDY OF DESTRUXIN-A, DESTRUXIN-B AND DESTRUXIN-E

The activities of three mycotoxins isolated from the hyphomycete Metarhizium anisopliae: destruxin A, B, and E (DA, DB and DE) are described and compared in vitro on leukemic cells. Their antitumor effect was investigated by flow cytometry on growth, cell viability and cell cycle perturbation 48 h after destruxin exposure. Against P388 leukemic cells, DE displayed greater antiproliferative activity than DA and DB. The minimum concentration required to inhibit 50% of cell proliferation is 0.33-mu-g/ml for DE, 11.7-mu-g/ml for DA and 9.4-mu-g/ml for DB. Cell cycle modifications were only observed with DE at 50 and 10-mu-g/ml and consisted in an accumulation of the cells in G0/1 phase. DA and DB did not modify the number of cells in G0/1 of the cell cycle. Nevertheless a decrease in the number of cells in G2 + M phase was induced by the three destruxins.