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Cytotoxic, immunosuppressive and trypanocidal activities of agrocybin, a polyacetylene produced by Agrocybe perfecta (Basidiomycota)

Rosa, Luiz H., Souza-Fagundes, Elaine M., Machado, Kátia M.G., Alves, Tânia M. A., Martins-Filho, Olindo A., Romanha, Alvaro J., Oliveira, Rodrigo C., Rosa, Carlos A., Zani, Carlos L.
World journal of microbiology & biotechnology 2006 v.22 no.6 pp. 539-545
Agrocybe, DNA fragmentation, Trypanosoma cruzi, apoptosis, bioassays, chromatography, cytotoxicity, ethyl acetate, flow cytometry, fractionation, fungi, humans, inhibitory concentration 50, kidneys, lymphocyte proliferation, melanoma, mice, mononuclear leukocytes, polyacetylenes, screening, temperature
The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was selected for further study in a screening of Brazilian basidiomycetes for bioactivity. The extract showed significant activity against the recombinant enzyme trypanothione reductase (TryR) from Trypanosoma cruzi, lymphocyte proliferation in human peripheral mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA), and the human cancer cell lines UACC-62 (melanoma), MCF-7 (mammary), and TK-10 (kidney). The chromatographic fractionation of the extract was monitored by the above bioassays and showed that agrocybin was the active component. Agrocybin, a known polyacetylene amide, showed an IC₅₀ of 2 μM in the TryR assay but killed only 60% of the trypomastigote form of T. cruzi in infected murine blood even at 680 μM. This weaker activity could be due to the low temperature used to mimic banked blood or as a consequence of its inactivation by blood, already reported in the literature. On the other hand, it inhibited the proliferation of PBMC by 50% at 3.4 μM and the growth of the cancer cell lines at concentrations between 9 and 24.5 μM. Measurements of DNA fragmentation using flow cytometry suggest that agrocybin promotes cell death via apoptosis.