In vitro effect of fungal cyclodepsipeptides on leukemic cells: study of destruxins A, B and 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 microgram/ml for DE, 11.7 micrograms/ml for DA and 9.4 micrograms/ml for DB. Cell cycle modifications were only observed with DE at 50 and 10 micrograms/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.
Odier
F
F
Station de Recherches de Pathologie Comparée, INRA CNRS URA 1184, Saint-Christol-les-Alès, France.
Vey
A
A
Bureau
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D047630:Depsipeptides; D005656:Fungal Proteins; D007399:Interphase / Q000187:drug effects; D007941:Leukemia P388 / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D005656:Fungal Proteins; D010456:Peptides, Cyclic; C040423:destruxin A; C040424:destruxin B; C040425:destruxin E